ESES 20Literatursammlung 202010 3 by 2rwZZG



  ESES Review of Recently Published Literature

                                            1                                    2
                  Collection: T. Clerici , T. Defechereux, F. Triponez
                           Compilation and design: U. Beutner
            1: Department of Surgery, Cantonal Hospital St. Gallen, St Gallen, Switzerland
 2: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland


                                Sep - Dez 2010
                  Data retrival from Pubmed: 11 Mar 2011

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Thyroid ......................................................................................... 2

Parathyroids .............................................................................. 41

Adrenals ..................................................................................... 55

NET ............................................................................................. 61

GI and General ........................................................................... 64

Pubmed-ID: PubMed-Identifier (unique number for each Pubmed entry
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                  opens the corresponding web site in browser (in Vista: CTRL-click).
Prophylactic Central Neck Dissection and Local Recurrence in Papillary Thyroid Cancer: a Meta-
Ann Surg Oncol, 17(12):3287-93.
Zetoune T, Keutgen X, Buitrago D, Aldailami H, Shao H, Mazumdar M, Fahey TJ, III, Zarnegar R. 2010.
BACKGROUND: The effectiveness of prophylactic central neck dissection (pCND) in the treatment of patients
with papillary thyroid carcinoma (PTC) to prevent local recurrence is controversial. We performed a meta-
analysis to assess the effect of pCND on local recurrence in PTC. METHODS: Exhaustive search of online
search engines identified five retrospective studies that compared the local recurrence rates of PTC in patients
without clinically detectable nodal disease in patients undergoing thyroidectomy + pCND (group A) to those
undergoing thyroidectomy alone (group B). A meta-analysis was performed by the fixed effects method.
Recurrence was documented by imaging, thyroglobulin detection, or reoperation. Location of recurrence was
identified in either the central or lateral neck compartment. RESULTS: A total of 1264 patients were included,
396 in group A and 868 in group B. Follow-up ranged from 6 months to 27 years. The overall recurrence rate
was 2.02% in group A versus 3.92% in group B (odds ratio [OR] = 1.05, 95% confidence interval [95% CI] 0.48-
2.31). The recurrence rate in the central neck compartment in group A was 1.86% compared to 1.68% in group
B (OR = 1.31, 95% CI 0.44-3.91). The recurrence rate in the lateral neck compartment in group A was 3.73%
compared to 3.79% in group B (OR = 1.21, 95% CI 0.52-2.75). There was no statistically significant difference in
the OR in the local recurrence between the two groups. CONCLUSIONS: This meta-analysis indicates that
pCND does not greatly reduce local recurrence in thyroid cancer. However, the available studies have
substantial limitations and a prospective multicenter study to determine the indications for pCND is warranted.
PubMed-ID: 20596784

Real-Time Elastography for the Differentiation of Benign and Malignant Thyroid Nodules: a Meta-
Thyroid, 20(10):1145-50.
Bojunga J, Herrmann E, Meyer G, Weber S, Zeuzem S, Friedrich-Rust M. 2010.
BACKGROUND: Work-up of thyroid nodules remains challenging. Fine-needle aspiration (FNA) has been shown
to be the most cost-effective way to select patients for surgery with sensitivities of 54%-90% and specificities of
60%-96% for the detection of malignant lesions. Ultrasound-based real-time elastography (RTE) enables the
determination of tissue elasticity and has shown promising results for the differentiation of thyroid nodules. A
meta-analysis was performed to assess the overall performance of RTE for the differentiation of thyroid nodules.
METHODS: Literature databases were searched. The inclusion criteria for studies were the use of FNA cytology
histopathology of surgical specimens as the diagnostic reference standard and assessment of sensitivity and
specificity of RTE. The meta-analysis was performed using an inverse variance method and the Der Simonian
and Laird Random effect estimator in case of established heterogeneity. RESULTS: Eight studies that included a
total of 639 thyroid nodules were analyzed. The overall mean sensitivity and specificity for the diagnosis of
malignant thyroid nodules by RTE of the eight studies was 92% confidence interval 88-96 and 90% confidence
interval 85-95, respectively. A significant heterogeneity was found for specificity of the different studies.
CONCLUSIONS: RTE has a high sensitivity and specificity in the evaluation of thyroid nodules. This technique
might be useful in conjunction or even instead of FNA to select patients with thyroid nodules for surgery.
PubMed-ID: 20860422

Randomized controlled trials
Incidence and Circumstances of Cervical Hematoma Complicating Thyroidectomy and Its Relationship
to Postoperative Vomiting.
Head Neck, 32(9):1173-7.
Bononi M, Amore BS, Vari A, Scarpini M, De CA, Miccini M, Meucci M, Tocchi A. 2010.
BACKGROUND: Cervical hematoma is hardly a predictable complication of thyroid surgery. Postoperative
vomiting has been reported as a likely risk factor. METHODS: Five hundred sixty-two patients undergoing

ESES Review of Recently Published Literature 2010-3                                                  Page 2 of 68
thyroidectomy were prospectively enrolled in the study and divided into 2 groups. Patients in group A received
ondansetron to prevent postoperative vomiting. In group B, patients with low vomiting risk received ondansetron
whereas patients at high risk received ondansetron plus dexamethasone. Postoperative outcomes of the groups
were analyzed and compared. RESULTS: Cervical hematomas developed in 3 patients (0.53%): 2 in group A
and 1 in group B. All hematomas occurred after 6 hours. The incidence of postoperative vomiting was 11.4% in
group A and 6.4% in group B (p = .04). CONCLUSION: Careful hemostasis remains of prime importance in
preventing cervical hematoma. Postoperative vomiting has not been confirmed by this study as a risk factor for
the development of hematoma. Ambulatory thyroid surgery is not advisable.
PubMed-ID: 20029984

Standard Versus Video-Assisted Thyroidectomy: Objective Postoperative Pain Evaluation.
Surg Endosc, 24(10):2415-7.
Miccoli P, Rago R, Massi M, Panicucci E, Metelli MR, Berti P, Minuto MN. 2010.
BACKGROUND: This prospective, randomized study was designed to objectively demonstrate that minimally
invasive video-assisted thyroidectomy (MIVAT) improves postoperative pain compared with standard
thyroidectomy, via the dosage of biochemical mediators measured before and after surgery. METHODS: Forty-
nine patients undergoing total thyroidectomy were allotted to MIVAT (n = 23) or traditional thyroidectomy (OPEN)
(n = 26) groups. At hospitalization (T0), interleukin (IL)-1, -2, -4, -6, -10, -3, tumor necrosis factor (TNF)-alpha,
TGF-beta, and MCP-1 were measured. The basal pain tolerance also was evaluated by VAS. Blood samples for
interleukin measurement and VAS evaluations were obtained from all patients in the recovery room (T1) and 24
h after surgery (T2). RESULTS: At T0, the MIVAT and the OPEN groups were not different in terms of basal pain
tolerance and biochemical profile. At T1, VAS scores were significantly higher (p = 0.04), whereas TGF-beta (p =
0.03) and MCP-1 (p = 0.03) levels were significantly lower in the OPEN than in the MIVAT group. No significant
difference was demonstrated for other interleukins. A significant inverse relationship between VAS and TGF-beta
was demonstrated and confirmed through the correlation (p = 0.003) and regression (p = 0.003, p < 0.0001, R
(2) = 0.172) coefficients; the stepwise regression also demonstrated that TGF was the most predictive factor of
postoperative pain (p = 0.0038) through an inverse relationship. No statistically significant difference has been
demonstrated at T2. CONCLUSIONS: TGF-beta serum levels immediately after surgery seem to correlate with
pain evaluation, confirming that reduced postoperative distress is an objective outcome of MIVAT. This result
confirms the results of studies based only on subjective pain evaluations.
PubMed-ID: 20195641

Perioperative Administration of Pregabalin for Pain After Robot-Assisted Endoscopic Thyroidectomy: a
Randomized Clinical Trial.
Surg Endosc, 24(11):2776-81.
Kim SY, Jeong JJ, Chung WY, Kim HJ, Nam KH, Shim YH. 2010.
BACKGROUND: Perioperative administration of pregabalin, which is effective for neuropathic pain, might reduce
early postoperative and chronic pain. This randomized, double-blinded, placebo-controlled trial (Clinical ID NCT00905580) was designed to investigate the efficacy and safety of pregabalin for reducing both
acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic
thyroidectomy. METHODS: Ninety-nine patients were randomly assigned to groups that received pregabalin 150
mg or placebo 1 h before surgery, with the dose repeated after 12 h. Assessments of pain and side effects were
performed 48 h postoperatively. The incidences of chronic pain and hypoesthesia in the anterior chest were
recorded 3 months after surgery. RESULTS: Ninety-four patients completed the study. Verbal numerical rating
scale scores for pain and the need for additional analgesics were lower in the pregabalin group (n = 47) than the
placebo group (n = 47) during 48 h postoperatively (P < 0.05). However, incidences of sedation and dizziness
were higher in the pregabalin group (P < 0.05). There were no differences between the groups in the incidences
of chronic pain and chest hypoesthesia at 3 months after surgery. CONCLUSIONS: Perioperative administration
of pregabalin (150 mg twice per day) was effective in reducing early postoperative pain but not chronic pain in
patients undergoing robot-assisted endoscopic thyroidectomy. Caution should be taken regarding dizziness and
PubMed-ID: 20376496

Bilateral Superficial Cervical Plexus Block Combined With General Anesthesia Administered in Thyroid
World J Surg, 34(10):2338-43.

ESES Review of Recently Published Literature 2010-3                                                   Page 3 of 68
Shih ML, Duh QY, Hsieh CB, Liu YC, Lu CH, Wong CS, Yu JC, Yeh CC. 2010.
BACKGROUND: We investigated the analgesic efficacy of bilateral superficial cervical plexus block in patients
undergoing thyroidectomy and to determine whether it reduces the adverse effects of general anesthesia.
METHODS: We prospectively recruited 162 patients who underwent elective thyroid operations from March 2006
to October 2007. They were randomly assigned to receive a bilateral superficial cervical block (12 ml per side)
with isotonic saline (group A; n = 56), bupivacaine 0.5% (group B; n = 52), or levobupivacaine 0.5% (group C; n
= 54) after induction of general anesthesia. The analgesic efficacy of the block was assessed with: intraoperative
anesthetics (desflurane), numbers of patients needing postoperative analgesics, the time to the first analgesics
required, and pain intensity by visual analog scale (VAS). Postoperative nausea and vomiting (PONV) for 24 h
were also assessed by the "PONV grade." We also compared hospital stay, operative time, and discomfort in
swallowing. RESULTS: There were no significant differences in patient characteristics. Each average end-tidal
desflurane concentration was 5.8, 3.9, and 3.8% in groups A, B, and C, respectively (p < 0.001). Fewer patients
in groups B and C required analgesics (A: B: C = 33:8:7; p < 0.001), and it took longer before the first analgesic
dose was needed postoperatively (group A: B: C = 82.1:360.8:410.1 min; p < 0.001). Postoperative pain VAS
were lower in groups B and C for the first 24 h postoperatively (p < 0.001). Incidences of overall and severe
PONV were lower, however, there were not sufficient numbers of patients to detect differences in PONV among
the three groups. Hospital stay was shorter in group B and group C (p = 0.011). There was no significant
difference in operative time and postoperative swallowing pain among the three groups. CONCLUSIONS:
Bilateral superficial cervical plexus block reduces general anesthetics required during thyroidectomy. It also
significantly lowers the severity of postoperative pain during the first 24 h and shortens the hospital stay.
PubMed-ID: 20623224

Other Articles
Cervical Hemorrhage Due to Spontaneous Rupture of the Superior Thyroid Artery: Case Report and
Review of the Literature.
Head Neck, 32(9):1277-81.
Stenner M, Helmstaedter V, Spuentrup E, Quante G, Huettenbrink KB. 2010.
BACKGROUND: Beneath the different reasons for cervical masses, a spontaneous hemorrhage presents a rare
and life-threatening condition. METHODS AND RESULTS: We present the rare case of a 62-year-old man who
was presented with a dramatically enlarging cervical mass causing respiratory distress because of upper airway
compression. An endotracheal intubation was lifesaving and avoided tracheotomy. A CT scan revealed a
hematoma in the region of the left external carotid artery. An emergency angiography embolized a ruptured
branch of the superior thyroid artery and surgery evacuated the hematoma. We discuss the rarity of the
condition, reasons for a spontaneous rupture of the artery, and the diagnostic and treatment strategy. In
addition, we review the literature on spontaneous thyroid artery hemorrhages, which, up to now, have been
described only for the inferior thyroid artery. CONCLUSION: We conclude that the optimal management for
cases of cervical hematoma is intubation, diagnosis, and angiography before surgery.
PubMed-ID: 19672961

Preoperative Predictors of Sternotomy Need in Mediastinal Goiter Management.
Head Neck, 32(9):1131-5.
Casella C, Pata G, Cappelli C, Salerni B. 2010.
BACKGROUND: The objective of this study was to identify the preoperative risk factors for patients in need of a
sternotomy in the management of mediastinal goiters in order to provide better preoperative planning and patient
consent. METHODS: We analyzed 98 patients who underwent surgery for mediastinal goiters (goiters extending
below the thoracic inlet > or =3 cm with the neck in hyperextension) between 1995 and 2008. Twelve (12.2%) of
the patients required a sternotomy. The patients' features were analyzed by the surgical approach performed.
Logistic regression analysis was used to study which variables were influencing the surgical strategy. The
receiver operating characteristic (ROC) curves were designed when appropriate. RESULTS: The analysis
disclosed the following risk factors: radiologic extension of mediastinal goiters below the aortic arch (odds ratio
[OR] = 32.87; 95% confidence interval [CI] = 4.04-267.12; p < .0001); posterior mediastinum involvement for
mediastinal goiters with subaortic extension (OR = 7.2; 95% CI = 1.52-34.14; p = .0244); history of mediastinal
goiters before surgery (for mediastinal goiters aged >160 months: OR = 22.8; 95% CI = 5.28-98.53; p < .0001).

ESES Review of Recently Published Literature 2010-3                                                  Page 4 of 68
CONCLUSIONS: Sternotomy need for mediastinal goiter removal can be predicted; in such cases surgeons
should not hesitate to perform it for minimizing complications.
PubMed-ID: 19953632

Differences in Serum Thyroglobulin Measurements by 3 Commercial Immunoradiometric Assay Kits and
Laboratory Standardization Using Certified Reference Material 457 (CRM-457).
Head Neck, 32(9):1161-6.
Lee JI, Kim JY, Choi JY, Kim HK, Jang HW, Hur KY, Kim JH, Kim KW, Chung JH, Kim SW. 2010.
BACKGROUND: Serum thyroglobulin (Tg) is essential in the follow-up of patients with differentiated thyroid
carcinoma (DTC). However, interchangeability and standardization between Tg assays have not yet been
achieved, even with the development of an international Tg standard (Certified Reference Material 457 [CRM-
457]). METHODS: Serum Tg from 30 DTC patients and serially diluted CRM-457 were measured using 3
different immunoradiometric assays (IRMA-1, IRMA-2, IRMA-3). The intraclass correlation coefficient (ICC)
method was used to describe the concordance of each IRMA to CRM-457. RESULTS: The serum Tg measured
by 3 different IRMAs correlated well (r > .85, p < .0001), but clinically relevant discrepancies were found in
13.3% of patients. IRMA-3, which claims to be standardized to CRM-457, showed the best ICC (p(1) = .98) for
the CRM-457. CONCLUSIONS: Hospitals caring for patients with DTC should either set their own cutoffs for
IRMAs for Tg based on their patient pools, or adopt IRMAs standardized to CRM-457 and calibrate their
laboratory using CRM-457.
PubMed-ID: 20029980

Investigation of Optimal Intensity and Safety of Electrical Nerve Stimulation During Intraoperative
Neuromonitoring of the Recurrent Laryngeal Nerve: a Prospective Porcine Model.
Head Neck, 32(10):1295-301.
Wu CW, Lu IC, Randolph GW, Kuo WR, Lee KW, Chen CL, Chiang FY. 2010.
BACKGROUND: Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has recently
been more frequently applied in thyroid surgery. However, concerns have been raised regarding the safety and
optimal intensity of electrical nerve stimulation. METHODS: Eight piglets were enrolled, and electrically evoked
electromyography (EMG) was recorded from the vocalis muscles via endotracheal surface electrodes. The
baseline EMG was measured and continuous pulsatile stimulations were performed on the vagus nerve and
RLN for 10 minutes. Changes of EMG waveform and cardiopulmonary status were analyzed. RESULTS: A
dose-response curve existed with increasing EMG amplitude as stimulating current was increased, with
maximum amplitude elicited on vagal and RLN stimulation at <1 mA. No obvious EMG changes and untoward
cardiopulmonary effects were observed after the stimulation. CONCLUSIONS: Electrical stimulation is safe
during IONM in this porcine model. Minimal current that required generating the maximal evoked EMG,
approximately 1 mA in this study, can be selected to minimize the risk of nerve damage and cardiopulmonary
PubMed-ID: 20091689

Minimally Invasive Video-Assisted Total Thyroidectomy: an Easy to Learn Technique for Skillful
Head Neck, 32(10):1370-6.
Papavramidis TS, Michalopoulos N, Pliakos J, Triantafillopoulou K, Sapalidis K, Deligiannidis N, Kesisoglou I,
Ntokmetzioglou I, Papavramidis ST. 2010.
BACKGROUND: Minimally invasive video-assisted total thyroidectomy (MIVATT) is a treating option for small
thyroids that demands skills required for both traditional thyroidectomy and endoscopic surgery. This prospective
study aims to define the learning curve for MIVATT for residents, with experience in traditional thyroid and
laparoscopic surgery. METHODS: In all, 36 MIVATTs for benign disease were evenly divided among 4 residents.
We recorded and analyzed: age, sex, pathology, thyroid weight, duration of the operation, DeltaCa
(postoperative minus preoperative calcemia), DeltaWBC (postoperative minus preoperative white blood cell
count), vocal motility, operative difficulty, postoperative vocal alteration, postoperative pain, complications, gram
of gland excised per minute of the operation, conversion, and hospitalization. RESULTS: Statistically significant
differences were observed in the different learning points, between duration of surgery (p < .001), operative
difficulty (p = .022), grams of gland excised per minute of operation (p < .001), and WBC (p = .011).
CONCLUSIONS: Surgeons that are experience in both thyroid and endoscopic surgery are subjects to a short
learning curve concerning MIVATT.

ESES Review of Recently Published Literature 2010-3                                                   Page 5 of 68
PubMed-ID: 20091694

Minimally Invasive Video-Assisted Thyroidectomy: Experience of 300 Cases.
Surg Endosc, 24(10):2393-400.
Fan Y, Guo B, Guo S, Kang J, Wu B, Zhang P, Zheng Q. 2010.
BACKGROUND: We report on patients selected for minimally invasive video-assisted thyroidectomy (MIVAT)
over a 3-year period and evaluate the feasibility and effects of this procedure. METHODS: Between March 2005
and August 2008, 300 patients (36 male, 264 female; mean age = 54.6 years) underwent MIVAT using a single
central incision with an average length of 2 cm (range = 1.5-3 cm), about 2 cm above the sternal notch. Small
conventional retractors and dissectors, ultrasonic scalpel, 5-mm laparoscope, and a video screen were the
instruments used. RESULTS: General anesthesia was used in 295 patients and regional block anesthesia in 5.
MIVAT was performed successfully in 280 patients (93.3%). Conversion to open thyroidectomy with a 4-cm-long
incision was required to achieve selective lymphadenectomy in 18 patients after frozen sections demonstrated
differentiated thyroid carcinoma. Only two patients with benign thyroid nodules were converted because of large
volume or massive hemorrhage from the upper pole vessels. Mean operative time was 35 min (range = 20-70
min) for unilateral lobectomy and 58 min (35-90 min) for bilateral thyroidectomy. No patients had wound
infections, postoperative bleeding that required reoperation, permanent hypoparathyroidism, or bilateral
recurrent laryngeal nerve palsy. However, permanent unilateral recurrent laryngeal nerve palsy appeared in five
cases (1.7%), transient unilateral recurrent laryngeal nerve palsy in seven (2.3%), superior laryngeal nerve injury
in five (1.7%), transient hypocalcemia in nine (3.0%), and mild skin burn from the ultrasonic scalpel in five
(1.7%). Postoperative pain was minimal and better cosmetic results were obtained than conventional open
thyroidectomy. Postoperative stay was shorter than with conventional open thyroidectomy. CONCLUSIONS:
MIVAT appears to be safe and feasible in patients with benign thyroid nodules, with minimal injury and excellent
cosmetic results. Furthermore, after properly lengthening the skin incision, MIVAT can be used for patients with
large benign thyroid nodules or even early-stage differentiated thyroid carcinoma.
PubMed-ID: 20177913

Prognostic Value of Histological and Immunohistochemical Characteristics for Predicting the
Recurrence of Medullary Thyroid Carcinoma.
Ann Surg Oncol, 17(9):2444-51.
Rios A, Rodriguez JM, Acosta JM, Balsalobre MD, Torregrosa N, Sola J, Perez-Flores D, Parrilla P. 2010.
INTRODUCTION: In medullary thyroid carcinoma, there is currently no consensus about the prognostic value of
histological and immunohistochemical parameters. This study was designed to analyze the value of various
histological and immunohistochemical characteristics for predicting the recurrence of medullary carcinoma.
METHODS: A total of 55 cases of medullary thyroid carcinoma have been reviewed. These were operated on
consecutively between 1971 and 2004 after histological confirmation. The data referring to clinical characteristics
and evolution were taken from the patient's clinical history. The macroscopic, microscopic, and
immunohistochemical characteristics of the tumors were taken from the pathological anatomy report. RESULTS:
In 14 (27%) cases, there was recurrence of the disease. The disease-free interval at 1 year was 88 +/- 5%; at 5
years 73 +/- 7%; at 10 years 73 +/- 7%; at 15 years 61 +/- 10%; and at 20 years or more 61 +/- 10%. Of the
histological parameters, only vascular invasion (0.0098) was related to a higher relapse rate. No epidemiological
variable or immunohistochemical marker was associated with relapse. However, it was found that staging (P =
0.0102), as well as tumor size (P = 0.0211) and lymph node affectation (P = 0.0012), are factors significantly
related to relapse of the disease. According to Cox's regression model, the only variable with a statistically
significant effect was vascular invasion (P = 0.0056; odds ratio = 5.2308). CONCLUSIONS: The overall
recurrence rate was 27%, and the main independent prognostic factor of recurrence was tumoral vascular
invasion at diagnosis. Staging, tumor size, and lymph node metastasis are prognostic factors of recurrence,
although they are not significant in the multivariate analysis.
PubMed-ID: 20224859

Retro-Auricular Video-Assisted "Gasless" Thyroidectomy: Feasibility Study in Human Cadavers.
Surg Endosc, 24(11):2895-9.
Walvekar RR, Wallace E, Bergeron B, Whitworth R, Beahm DD, Nuss DW. 2010.
BACKGROUND: In recent years, there has been a surge of interest in developing alternative surgical
approaches to the thyroid gland with a focus on cosmesis. Approaches can be either complete endoscopic
approaches using CO(2) insufflation or endoscopy-assisted approaches. We describe a novel approach for

ESES Review of Recently Published Literature 2010-3                                                  Page 6 of 68
thyroidectomy via a retro-auricular incision without gas insufflation using endoscopic assistance. METHODS: Six
fresh human cadavers were utilized. Four head and neck specimens were used to assess the retro-auricular
approach and the creation of surgical space in the lower neck. Three hemithyroidectomy in two fresh human
cadavers procedures were performed via a retro-auricular approach. The end-point of the study was successful
removal of the hemithyroid gland with preservation of the recurrent laryngeal nerve. RESULTS: In all cases, the
retro-auricular flap and subplatysmal plane could be achieved without difficulty. Three hemithyroid specimens
were successfully removed in two cadaveric specimens using the retro-auricular approach with endoscopic
guidance. Thyroid gland resection with identification and preservation of the recurrent laryngeal nerve could be
achieved in all three procedures (100%). CONCLUSION: The retro-auricular approach or the "Walvekar
approach" permits adequate working space and an excellent endoscopic surgical view for removal of the
ipsilateral hemithyroid gland with an option for a bilateral approach using a "gasless technique.".
PubMed-ID: 20419321

Utilization of Total Thyroidectomy for Differentiated Thyroid Cancer in Children.
Ann Surg Oncol, 17(10):2545-53.
Raval MV, Bentrem DJ, Stewart AK, Ko CY, Reynolds M. 2010.
PURPOSE: Recent recommendations suggest that total thyroidectomy (TT) is the surgical management of
choice for differentiated thyroid cancer in children. The objective of this study is to assess trends in extent of
surgical resection for differentiated thyroid cancer in children over the past two decades and to identify patient,
tumor or hospital factors associated with use of TT. PATIENTS AND METHODS: Of 8,013 patients (aged 0-21
years) with differentiated thyroid cancer from the National Cancer Data Base (1985-2007), 5,933 (74%)
underwent TT. Trends in extent of surgery were examined. Logistic regression was used to identify factors that
predict use of TT. RESULTS: Use of TT increased from 50.6% in 1985 to 84% in 2007 (P < 0.001). Patients
were more likely to undergo TT if they had higher household income or had private insurance (P = 0.002 and P =
0.037). Patients were more likely to undergo TT if they had larger tumors or if there were nodal metastases
present at time of resection (both P < 0.001). After adjusting for patient and tumor factors, patients treated at
high-volume or Children's Oncology Group hospitals were more likely to undergo TT than patients treated at low-
volume or non-Children's Oncology Group hospitals (P < 0.001). CONCLUSIONS: Overall utilization of TT in
children with differentiated thyroid cancer has steadily increased over the past 23 years in the USA. Variations in
use of TT are not only related to tumor factors including size and nodal involvement, but also are also related to
socioeconomic and hospital factors, demonstrating disparities in care.
PubMed-ID: 20429037

[Postoperative Hypoparathyroidism: Risk Factors and Out-Patient Management Following Thyroid
Postoperativer Hypoparathyreoidismus: Risikofaktoren Und Ambulante Nachsorge Nach
Chirurg, 81(10):909-14.
Franzke T, Fromke C, Jahne J. 2010.
BACKGROUND: Postoperative hypoparathryroidism is the most common complication following thyroid
resection. Currently the data about the quality of out-patient management is inadequate. PATIENTS AND
METHODS: Between 2003 and 2006 a total of 1,966 resections were performed and retrospectively analyzed.
RESULTS: Of the patients 14% developed temporary hypoparathyroidism and permanent hypoparathyroidism
was seen in 0.37%. The extent of resection and female sex were significant risk factors. The recommendation to
wean calcium substitution was only performed in 18% of affected patients. CONCLUSION: The results
demonstrated that the quality of out-patient management in cases of postoperative hypoparathyroidism after
thyroid resection is insufficient.
PubMed-ID: 20464355

Differences in Postoperative Outcomes, Function, and Cosmesis: Open Versus Robotic Thyroidectomy.
Surg Endosc , 24(12):3186-94.
Lee J, Nah KY, Kim RM, Ahn YH, Soh EY, Chung WY. 2010.
BACKGROUND: Robotic thyroidectomy using a gasless transaxillary approach, first described in 2008, has
become popular. This study compared outcomes, including postoperative distress and patient satisfaction, for
patients undergoing robotic thyroidectomy with those for patients treated by conventional open thyroidectomy.
METHODS: Of 84 prospectively enrolled patients, 41 underwent robotic thyroidectomy (the robot group), and 43

ESES Review of Recently Published Literature 2010-3                                                  Page 7 of 68
received conventional open thyroidectomy (the open group). All the patients were followed up for at least 3
months after surgery. Videolaryngostroboscopic examinations were performed preoperatively and after 1 week
and after 3 months postoperatively. Postoperative pain and discomfort were evaluated using a symptom scale.
Subjective voice and swallowing changes were assessed by questionnaires; and satisfaction with cosmetic
outcome was measured by verbal response at 3 months. RESULTS: The two groups were similar in age,
gender, type of operation, and final pathologic diagnosis. Although the mean operating time was significantly
longer with the robotic technique than with open surgery, there were no between-group differences in
postoperative pain or duration of hospital stay. No patient in either group experienced any major postoperative
complication. Postoperative discomfort in the neck and swallowing disturbances were significantly more frequent
in the open group than in the robot group, both at 1 week and at 3 months after surgery. However, there was no
significant between-group difference in subjective voice parameters. At 3 months, the mean cosmetic
satisfaction score was significantly higher in the robotic than in the open group. CONCLUSION: Although
postoperative pain levels and complications were comparable in the two groups, conventional open
thyroidectomy requires a shorter operative time. The robotic technique, however, offers several distinct
advantages including very good to excellent cosmetic results, reduced postoperative neck discomfort, and fewer
adverse swallowing symptoms.
PubMed-ID: 20490558

The Relationship Between Body Mass Index and Thyroid Cancer Pathology Features and Outcomes: a
Clinicopathological Cohort Study.
J Clin Endocrinol Metab, 95(9):4244-50.
Paes JE, Hua K, Nagy R, Kloos RT, Jarjoura D, Ringel MD. 2010.
BACKGROUND: Obesity has been implicated as a predisposing and disease-modifying factor in cancer.
Epidemiological studies suggest that obesity is associated with an increased risk of thyroid cancer; however, the
relationships between obesity and thyroid cancer stage or behavior are uncertain. We hypothesized that a higher
body mass index (BMI) would be associated with aggressive thyroid cancer features and a higher incidence of
persistent/recurrent disease. METHODS: Two hundred fifty-nine consecutive patients with thyroid cancer were
enrolled in this retrospective cohort study. Histopathological tumor features, stage at diagnosis, and disease
status during and at the end of the study were determined based on chart review. BMI was calculated at the first
clinical visit to our institution. The relationships between BMI and these parameters were assessed. RESULTS:
Mean follow-up time for the group was 6.2 yr (0.11-46 yr). No positive associations were identified between BMI
and T, N, or M stage at diagnosis, vascular invasion, or recurrent or persistent disease on univariate or
multivariate analyses. The absence of an association was also demonstrated on analysis by BMI quartiles. An
unexpected inverse association was identified between BMI and nodal metastasis and tumor invasion on both
univariate and multivariate analyses, suggesting that obesity may be associated with less aggressive tumor
features, a finding that requires confirmatory studies. CONCLUSION: Although obesity has been associated with
increased thyroid cancer incidence, a higher BMI was found not to be associated with more aggressive tumor
features or a greater likelihood of recurrence or persistence over the analyzed time period.
PubMed-ID: 20519347

A Decrease of Calcitonin Serum Concentrations Less Than 50 Percent 30 Minutes After Thyroid Surgery
Suggests Incomplete C-Cell Tumor Tissue Removal.
J Clin Endocrinol Metab, 95(9):E32-E36.
Faggiano A, Milone F, Ramundo V, Chiofalo MG, Ventre I, Giannattasio R, Severino R, Lombardi G, Colao A,
Pezzullo L. 2010.
CONTEXT AND OBJECTIVES: The prognosis of medullary thyroid carcinoma (MTC) depends on the
completeness of the first surgical treatment. To date, it is not possible to predict whether the tumor has been
completely removed after surgery. The aim of this study was to evaluate the reliability of an intraoperative
calcitonin monitoring as a predictor of the final outcome after surgery in patients with MTC. PATIENTS AND
METHODS: Twenty patients underwent total thyroidectomy and central lymph node dissection on the basis of a
positive pentagastrin test. In six cases a preoperative diagnosis of MTC was achieved at the cytological
examination. During the surgical intervention, calcitonin was measured at the time of anesthesia, at the time of
manipulation, and 10 and 30 min after surgical excision. At the histological examination, 10 patients had MTC
and 10 had C cell hyperplasia. RESULTS: As compared with calcitonin levels before thyroidectomy, a decrease
of calcitonin greater than 50% 30 min after surgery was able to significantly distinguish patients who were cured
from those who experienced persistence of disease. It was not possible to find a similar result when the
decrease of calcitonin 10 min after surgery was considered. CONCLUSIONS: A rate of calcitonin decrease less

ESES Review of Recently Published Literature 2010-3                                                 Page 8 of 68
than 50% 30 min after thyroidectomy plus central neck lymph node dissection suggests the persistence of tumor
tissue in patients operated for MTC. These results indicate that intraoperative calcitonin monitoring may be a
useful tool to predict the completeness of surgery in patients with MTC.
PubMed-ID: 20534767

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European
Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of
Thyroid Nodules.
J Endocrinol Invest, 33(5 Suppl):1-50.
Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedus L, Vitti P. 2010.
American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid
Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are
systematically developed statements to assist health care professionals in medical decision making for specific
clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional
judgment was applied. These guidelines are a working document that reflects the state of the field at the time of
publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage
medical professionals to use this information in conjunction with their best clinical judgment. Any decision by
practitioners to apply these guidelines must be made in light of local resources and individual patient
PubMed-ID: 20543550

Rehospitalization Among Elderly Patients With Thyroid Cancer After Thyroidectomy Are Prevalent and
Ann Surg Oncol, 17(11):2816-23.
Tuggle CT, Park LS, Roman S, Udelsman R, Sosa JA. 2010.
BACKGROUND: Thyroid cancer increases in incidence and aggressiveness with age. The elderly are the fastest
growing segment of the U.S. population. Reducing rates of rehospitalization would lower cost and improve
quality of care. This is the first study to report population-level information characterizing rehospitalization after
thyroidectomy among the elderly. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-
Medicare-linked database was used to identify patients older than aged 65 years with thyroid cancer who
underwent thyroidectomy from 1997-2002. Patient and hospital characteristics were studied to predict the risk of
rehospitalization. Outcomes were 30-day unplanned rehospitalization rate, cost, and length of stay (LOS) of
readmission. RESULTS: Of 2,127 patients identified, 69% were women, 84% had differentiated thyroid cancer,
and 52% underwent total thyroidectomy. Mean age was 74 years. A total of 171 patients (8%) underwent 30-day
unplanned rehospitalization. Rehospitalization was associated with increased comorbidity, advanced stage,
number of lymph nodes examined, increased LOS of index admission, and small hospital size (all P < 0.05).
Patients with a complication during index hospital stay were more likely to be readmitted (P < 0.001), whereas
patients who saw an outpatient medical provider after index discharge returned less frequently (P < 0.001).
Forty-seven percent of readmissions were for endocrine-related causes. Mean LOS and cost of rehospitalization
were 3.5 days and $5,921, respectively. Unplanned rehospitalization was associated with death at 1 year
compared with nonrehospitalized patients (18% vs. 6%; P < 0.001). DISCUSSION: Rehospitalization among
Medicare beneficiaries with thyroid cancer after thyroidectomy is prevalent and costly. Further study of predictors
could identify high-risk patients for whom enhanced preoperative triage, improved discharge planning, and
increased outpatient support might prove cost-effective.
PubMed-ID: 20552406

Sentinel Lymph Node Biopsy for Papillary Thyroid Cancer: 12 Years of Experience at a Single Institution.
Ann Surg Oncol, 17(11):2970-5.
Cunningham DK, Yao KA, Turner RR, Singer FR, Van Herle AR, Giuliano AE. 2010.
BACKGROUND: The purpose of this study was to report our experience with sentinel lymph node dissection
(SLND) for papillary thyroid carcinoma, to evaluate the feasibility and safety of the procedure, and to examine its
potential utility as a guide for central neck dissection. MATERIALS AND METHODS: A retrospective chart review
of patients undergoing total thyroidectomy from January 1998 thru January 2010 was conducted. Intratumoral
injection of blue dye was used to identify the SLN. Central neck dissection (CND) was performed if the SLN was
positive on frozen section. Locally advanced disease, previous thyroid surgery, or lymphadenopathy on
preoperative imaging or intraoperative palpation were exclusion criteria. RESULTS: A total of 211 patients
underwent SLN mapping. Of these, 165 patients (78%) were female and 46 (22%) were male. Also, 75 (36%)

ESES Review of Recently Published Literature 2010-3                                                    Page 9 of 68
were </=45 years of age, and 136 (64%) were older than 45. Tumors were </=2.0 cm (T1) in 142 patients (67%),
2-4 cm (T2) in 35 patients (17%), >4 cm with minimal invasion (T3) in 32 patients (15%), and locally invasive
(T4) in 2 patients (1%). At least 1 blue node was found in 192 patients (91%). Also, 47 patients had a positive
SLN on frozen section, with an additional 24 node-positive patients on permanent section, for a total of 71
(37%). There were 43 patients (91%) who underwent central neck dissection; 26 (60%) had additional
metastases. CONCLUSIONS: Sentinel lymphadenectomy for papillary thyroid carcinoma is feasible, safe, and
can identify patients who may benefit from central neck dissection.
PubMed-ID: 20552407

Endoscopic Thyroidectomy Via Breast Approach for Patients With Graves' Disease.
World J Surg, 34(9):2228-32.
Li ZY, Wang P, Wang Y, Xu SM, Cao LP, Que RS. 2010.
BACKGROUND: Endoscopic thyroidectomy via breast approach provides excellent results from a cosmetic
viewpoint. We applied this procedure to Graves' disease and evaluated its feasibility and outcomes. METHODS:
From May 2006 to November 2009, a total of 37 patients (34 women and 3 men) with Graves' disease were
included in this study. Bilateral subtotal thyroidectomy, which left behind 4-6 g of thyroid remnant, was the
standard procedure. For markedly enlarged goiter, fractional resection was performed. RESULTS: This
procedure was performed successfully in all 37 patients. The mean operative time, mean blood loss, and mean
excised thyroid weight were 84.7 min, 64 ml, and 51.8 g, respectively. Fractional resection was performed in six
cases, where the mean operative time, mean blood loss, and mean excised thyroid weight were 119 min, 138.3
ml, and 102.2 g, respectively. Postoperative transient hypocalcemia occurred in 5 cases (13.5%), and no other
complications were noted. The average postoperative hospital stay was 3.4 (range, 3-5) days. One case
experienced recurrent hyperthyroidism during a mean follow-up period of 13 months. All patients were satisfied
with the cosmetic result of the procedure. CONCLUSIONS: Endoscopic subtotal thyroidectomy performed via
breast approach is a technically feasible and safe procedure with excellent cosmetic results for patients with
Graves' disease. In patients with markedly enlarged thyroid glands, subtotal thyroidectomy can be achieved
through a fractional resection strategy.
PubMed-ID: 20556611

Improved Detection Does Not Fully Explain the Rising Incidence of Well-Differentiated Thyroid Cancer: a
Population-Based Analysis.
Am J Surg, 200(4):454-61.
Morris LG, Myssiorek D. 2010.
BACKGROUND: The increasing incidence of thyroid cancer may be an artifact of increased diagnostic scrutiny,
permitting detection of smaller, subclinical thyroid cancers. Our objective was to examine trends in the incidence
of well-differentiated thyroid cancers with large size and adverse pathological features. METHODS: Detailed
population-based analysis of incidence trends in well-differentiated thyroid carcinoma (1973-2006) in the
Surveillance Epidemiology and End Results (SEER) cancer registry, using weighted least squares and Joinpoint
regression models. RESULTS: The incidence of well-differentiated thyroid cancer (WDTC) in the United States
has tripled since 1973 (P < .0001). Incidence trends differ significantly between geographic regions and racial
groups. Large WDTCs, including those >4 cm or >6 cm, have more than doubled in incidence (P < .0001).
Cancers with extrathyroidal extension and with cervical metastases have also more than doubled in incidence (P
< .0001). CONCLUSIONS: While the model of improving screening does explain increased diagnoses of small
thyroid cancers, significant rises in the incidence of large cancers, and cancers with clinically significant
pathological adverse features, are harder to explain. Alternative hypotheses, including a true increase in cancer
incidence, would seem to merit exploration.
PubMed-ID: 20561605

The Tale of Radioiodine and Graves' Orbitopathy.
Thyroid, 20(7):785-93.
Ponto KA, Zang S, Kahaly GJ. 2010.
BACKGROUND: Autoimmunity against the thyrotropin receptor (TSH-R) is a key pathogenic element in Graves'
disease (GD) and the autoimmune aberration may be modified by antithyroid treatment. An association between
radioactive iodine (RAI) therapy for GD and the development or worsening of Graves' orbitopathy (GO) is widely
quoted. RAI-associated leakage of thyroid antigen(s) leads to an increased production of TSH-R antibodies that
may initiate the eye injury. SUMMARY: RAI therapy leads to prolonged worsening of autoimmunity against the

ESES Review of Recently Published Literature 2010-3                                                Page 10 of 68
TSH-R, and the number of patients entering remission of TSH-R autoimmunity is considerably lower than with
other antithyroid therapies. Scientific evidence has indicated that RAI treatment for GD is associated with
increased risk of occurrence or progression of GO compared with antithyroid drugs (ATD) and thyroid surgery.
The risks of developing new GO or worsening of preexisting GO is around 20% after RAI and around 5% after
ATD. The risk of developing severe GO after RAI is around 7%. Smoking, high levels of pretreatment serum
triiodothyronine, and post-RAI hypothyroidism are associated with increased risk of GO, whereas a high TSH-R
autoantibody titer is an independent risk factor for the progression of GO. In patients with mild preexisting GO,
steroid prophylaxis is effective in preventing deterioration of GO. Also, routine use of prophylactic oral steroids
with RAI therapy should be considered in GD patients without overt GO, but even more so in those at higher
risks of eye complications such as smokers, old men, and those with severe hyperthyroidism or high TSH-R
antibody titers. CONCLUSION: In contrast to ATD, remission of TSH-R autoimmunity after RAI therapy is less
common, and RAI for GD is associated with definite increased risk of GO. Oral steroids are beneficial for
patients with preexisting GO, particularly smokers.
PubMed-ID: 20578895

The Thyroid Gland in Works of Famous Old Anatomists and Great Artists.
Langenbecks Arch Surg, 395(7):973-85.
Ignjatovic M. 2010.
BACKGROUND: The thyroid gland has always been known, but its function was unclear for a long time. It has
been thought to be a part of the larynx, protection of the larynx, a lubricant gland, an esthetic organ, and a buffer
preventing quick afflux of blood into the head. The aim of this work is to bring out the thyroid gland in works of
famous old anatomists and great artists, without valorization of its precisions and exactitudes. METHODS: The
works of old anatomists and great artists are analyzed. RESULTS: There are presentations in works of
anatomists such as: Rhazes, Avicenna, Mansur, Arderne, da Vinci, Vesalius, Casseri, Bidloo, Cowper,
Morgagni, Haller, Gautier d'Agoty, Monro, Mascagni, Bell, Scarpa, Cloquet, Bourgery, etc. Also, there are artistic
works with accentuation of thyroid gland, such as the works of: da Vinci, Botticelli, Durer, Titian, Caravaggio,
Rubens, Rembrandt, Manet, etc. CONCLUSION: Thyroid gland has been rarely presented in the works of old
anatomists. Working as illustrators of anatomy, these great artists have had an invaluable importance for the
development of anatomic knowledge, and some of their works are a subject of examination even in our time.
PubMed-ID: 20607550

Primary Thyroid Lymphoma (Correction of Lympoma): Diagnostic and Therapeutic Dilemmas.
Surg Oncol, 19(4):e124-e129.
Sakorafas GH, Kokkoris P, Farley DR. 2010.
Primary thyroid lymphomas (PTL) are very rare tumors, typically presenting as a rapidly enlarging, painless
thyroid mass, which may cause pressure symptoms of the aerodigestive tract. Preoperative diagnosis can be
established by using modern imaging methods (mainly ultrasonography) and FNA with immunohistochemistry
and flow cytometry. Open (surgical) biopsy may be indicated to confirm the diagnosis and identify the subtype of
PTL. Therapeutic strategies are distinct from other thyroid malignancies, and include local therapy alone
(surgery or radiotherapy or surgery plus radiotherapy) or - most commonly - combined multimodality treatment
(mainly chemoradiation therapy). Management should be tailored to the individual patient; treatment-related
morbidity should be taken into account. A high index of suspicion from the part of the clinician is required to
achieve early diagnosis and prompt treatment of this potentially curable thyroid malignancy.
PubMed-ID: 20620043

Thyroid Nodules; Interpretation and Importance of Fine-Needle Aspiration (FNA) for the Clinician -
Practical Considerations.
Surg Oncol, 19(4):e130-e139.
Sakorafas GH. 2010.
Thyroid nodules are very common lesions. Despite that the great majority is benign, in a significant percentage
of them there is an underlying malignancy. Malignant thyroid nodules should be managed surgically, while the
more common benign thyroid nodules may be managed conservatively. A systemic and careful diagnostic
evaluation is needed to recognize nodules (overtly malignant or with malignant potential), and to avoid
unnecessary surgery in a large percentage of patients with benign disease. Fine-needle aspiration (FNA) has a
central role in the diagnostic investigation of the patient with thyroid nodules. FNA is a safe, useful, and cost-
effective procedure. To increase accuracy, FNA can be performed under ultrasonographic guidance (if needed).

ESES Review of Recently Published Literature 2010-3                                                   Page 11 of 68
Its results may be particularly helpful in determining the indication for surgery. In contrast, the role of FNA in
selecting the extent of surgery is limited today. This is due to the fact that during the last decade there is a clear
trend toward radical surgical management of thyroid nodular disease (both benign and malignant) by total/near-
total thyroidectomy.
PubMed-ID: 20620044

Establishment of an Intraoperative Staging System (IStage) by Improving UICC TNM Classification
System for Papillary Thyroid Carcinoma.
World J Surg, 34(11):2570-80.
Ito Y, Ichihara K, Masuoka H, Fukushima M, Inoue H, Kihara M, Tomoda C, Higashiyama T, Takamura Y,
Kobayashi K, Miya A, Miyauchi A. 2010.
BACKGROUND: Papillary thyroid carcinoma generally has an indolent nature, but cases demonstrating certain
features are progressive. UICC TNM classification is the most widely adopted system to evaluate the biological
behavior of this carcinoma, but it is doubtful whether this system that evaluates only the preoperative findings
can appropriately reflect patient prognosis. In this study, we established a new staging system (iStage) based on
not only preoperative but also intraoperative findings. METHODS: We investigated the prognoses of 5,911
patients with papillary carcinoma without distant metastasis at diagnosis who underwent initial surgery between
January 1987 and January 2005 and compared the utility of iStage with that of conventional classification
systems, such as UICC Stage, MACIS score (>7 and </=7), AMES, and CIH classification. RESULTS: Disease-
free survival (DFS) and cause-specific survival (CSS) of patients with stage IVA were better than those of high-
risk patients on other systems, and CSS of stage III patients did not differ from stage IVA patients. We
established iStage by improving the original UICC stage. We set cutoff age to 55 years, instead of 45. Patients
showing significant, not minimal, extrathyroid extension on intraoperative findings underwent T upgrading: tumor
size 2 cm or smaller to T3 and larger than 2 cm to T4a. N classification was revised based on the size of node
metastasis and extranodal tumor extension: N0, no preoperatively detected regional node metastasis; N1,
preoperatively detected regional node metastasis measuring 3 cm or less and without extranodal tumor
extension on intraoperative findings; N2, regional node metastasis >3 cm or having extranodal tumor extension
on intraoperative examination. Five-year and 10-year DFS and CSS of iStage IVA patients were worse than
high-risk patients on other classification systems, and iStage III patients showed a worse DFS, but not CSS, than
iStage I or II patients. CONCLUSIONS: We established a new classification system, iStage, based not only on
preoperative but also on intraoperative findings, which has high utility. Appropriate intraoperative evaluation is
mandatory to grade biological characteristics, including prognosis, of papillary carcinoma.
PubMed-ID: 20625728

Clinical Outcomes of Patients With Papillary Thyroid Carcinoma After the Detection of Distant
World J Surg, 34(10):2333-7.
Ito Y, Higashiyama T, Takamura Y, Kobayashi K, Miya A, Miyauchi A. 2010.
PURPOSE: Papillary thyroid carcinoma generally has an excellent prognosis but can have recurrence to the
distant organs that is often life-threatening. To date, prognosis and prognostic factors of papillary carcinoma
have been intensively investigated, but our knowledge regarding prognosis after the detection of distant
recurrence remains inadequate. METHODS: We investigated the prognosis and prognostic factors of papillary
carcinoma after distant recurrence was detected during follow-up in a series of 105 patients who underwent
locally curative surgery between 1987 and 2004. RESULTS: To date, 30 patients (29%) have died of carcinoma,
and the 5-year and 10-year cause-specific survival (CSS) rates after the detection of distant recurrence were 71
and 50%, respectively. Patients aged 55 years or older at recurrence or with massive extrathyroid extension of
primary lesions demonstrated a significantly worse CSS. On multivariate analysis, these two parameters were
recognized as independent prognostic factors. Gender, tumor size, and lymph node metastasis did not affect
patient prognosis. Uptake of radioactive iodine (RAI) to distant metastasis was not significantly linked to CSS,
but none of the patients younger than aged 55 years showing RAI uptake died of carcinoma. Appearance of
distant recurrence to organs other than lung also predicted a dire prognosis. CONCLUSIONS: Age at recurrence
and extrathyroid extension of primary lesions were significantly related to patient prognosis after the detection of
distant recurrence. RAI therapy is effective, especially for younger patients, if metastatic lesions show RAI
PubMed-ID: 20628741

ESES Review of Recently Published Literature 2010-3                                                    Page 12 of 68
Evaluation of Postoperative Pain After Minimally Invasive Video-Assisted and Conventional
Thyroidectomy: Results of a Prospective Study. ESES Vienna Presentation.
Langenbecks Arch Surg, 395(7):845-9.
Alesina PF, Rolfs T, Ruhland K, Brunkhorst V, Groeben H, Walz MK. 2010.
BACKGROUND: One of the advocated benefits of minimally invasive video-assisted thyroidectomy (MIVAT) is
reduction of postoperative pain. We compared in a prospective study pain after video-assisted and conventional
thyroidectomy (CT). METHODS: One hundred sixty-nine patients (56 men, 113 women, mean age: 50 +/- 14
years) operated between November 2007 and February 2008 were included. MIVAT was performed if thyroid
volume was <30 ml or the nodule diameter < 35 mm. Postoperative pain scores were documented on a visual
analog scale (VAS; 0 = no and 100 = unbearable pain) at 8, 24, 36, and 48 h after surgery. Additionally,
postoperative analgesic consumption was registered. RESULTS: Seventy-five patients (17 men, 58 women,
mean age: 45 +/- 15 years) underwent MIVAT and 94 (39 men, 55 women, mean age: 54 +/- 15 years) CT. The
mean overall VAS score at 8, 24, 36 and 48 h did not significantly differ between the groups (26 +/- 21 vs. 26 +/-
19 at 8 h, 17 +/- 15 vs. 21 +/- 18 at 24 h, 11 +/- 13 vs. 10 +/- 11 at 36 h and 7 +/- 12 vs. 6 +/- 8 at 48 h in MIVAT
and CT group, respectively) [p = ns]. Twelve vs. 13 patients (16% vs. 14%) required opioid administration on the
day of the operation [p = ns]. CONCLUSIONS: The length of the skin incision seems not to influence the
perception of pain after thyroid surgery.
PubMed-ID: 20628756

Correlation Between the BRAF V600E Mutation and Tumor Invasiveness in Papillary Thyroid Carcinomas
Smaller Than 20 Millimeters: Analysis of 1060 Cases.
J Clin Endocrinol Metab, 95(9):4197-205.
Basolo F, Torregrossa L, Giannini R, Miccoli M, Lupi C, Sensi E, Berti P, Elisei R, Vitti P, Baggiani A, Miccoli P.
CONTEXT: Evaluation of the degree of neoplastic infiltration beyond the thyroid capsule remains a unique
parameter that can be evaluated by histopathological examination to label a papillary thyroid carcinoma (PTC) of
20 mm or less in size as a pT1 or pT3 tumor. OBJECTIVE: We correlated the BRAF V600E mutation with both
clinical-pathological features and the degree of neoplastic infiltration to redefine the reliability of the actual
system of risk stratification in a large selected group of PTCs smaller than 20 mm. DESIGN: The presence of
BRAF mutations was examined in 1060 PTCs less than 20 mm divided into four degrees of neoplastic infiltration:
1) totally encapsulated; 2) not encapsulated without thyroid capsule invasion; 3) thyroid capsule invasion; and 4)
extrathyroidal extension. RESULTS: The overall frequency of the BRAF V600E mutation was 44.6%. In both
univariate and multivariate analyses, BRAF mutations showed a strong association with PTC variants (classical
and tall cell), tumor size (11-20 mm), multifocality, absence of tumor capsule, extrathyroidal extension, lymph
node metastasis, higher American Joint Commission on Cancer stage, and younger patient age. In PTCs staged
as pT1 with thyroid capsule invasion, the frequency of BRAF mutations was significantly higher than in pT1
tumors that did not invade the thyroid capsule (67.3 vs. 31.8%, respectively; P < 0.0001). No statistically
significant difference in BRAF alterations was found between pT1 tumors with thyroid capsule invasion and pT3
tumors (67.3 and 67.5%, respectively). CONCLUSION: We suggest that evaluation of BRAF status would be
useful even in pT1 tumors to improve risk stratification and patient management, although follow-up data are
necessary to confirm our speculations.
PubMed-ID: 20631031

Radio-Guided Excision of Metastatic Lymph Nodes in Thyroid Carcinoma: a Safe Technique for
Previously Operated Neck Compartments.
World J Surg, 34(11):2581-8.
Erbil Y, Sari S, Agcaoglu O, Ersoz F, Bayraktar A, Salmaslioglu A, Gozkun O, Adalet I, Ozarmagan S. 2010.
BACKGROUND: Better follow-up of patients with papillary thyroid cancer (PTC) and more sensitive detection
leads to detection of recurrences in the neck. Despite excellent outcomes, the major challenge is controlling
locoregional recurrence. We aimed to investigate whether the radio-guided excision of metastatic lymph nodes
makes it possible to find the affected lymph nodes in patients with previously operated neck compartments.
METHOD: This prospective study included 46 patients with recurrent/persistent PTC who had previously
undergone operation of the neck compartment. Prior to operation, the pathologic node was localized by
ultrasound (US) and radiotracer ((99m)Tc-labeled rhenium colloid) was injected directly into the pathologic node.
Careful dissection was carried out following the area of maximum radioactivity until the metastatic lymph node(s)
were identified and excised. RESULT: One affected lymph node was removed in 17 patients, and more than one
lymph node (affected or additional nodes) was removed in 29 patients. The median count from the lesion was

ESES Review of Recently Published Literature 2010-3                                                   Page 13 of 68
significantly higher than values from the lesion bed (background activity) (16,886 counts/20 s versus 52
counts/20 s; p < 0.001). During follow-up, four patients were lost to follow-up and 27 patients had negative US
and basal thyroglobulin (Tg). Five patients had suspicious lymph nodes on the operated side. Although the basal
Tg level remained above the normal limit, moderately high in 8 patients, no metastases were detected in the
neck. CONCLUSIONS: Radio-guided excision of metastatic lymph nodes can be performed safely for the
detection and excision of recurrent thyroid cancer in the central and lateral neck.
PubMed-ID: 20632005

Real-Time Ultrasound Elastography--a Noninvasive Diagnostic Procedure for Evaluating Dominant
Thyroid Nodules.
Langenbecks Arch Surg, 395(7):865-71.
Vorlander C, Wolff J, Saalabian S, Lienenluke RH, Wahl RA. 2010.
PURPOSE: Ultrasound elastography (USE) is a newly developed technique for the evaluation of tissue stiffness.
It is known that malignancies often show a low-strain value. So far, only limited data for thyroid nodules is
available. METHODS: This study included 309 prospective evaluated patients with dominant, nontoxic thyroid
nodules. All patients were referred to surgery. USE was performed preoperatively. Three measuring groups were
formed: hard (< 0.15), intermediate (0.16-0.3), and soft (> 0.31). The measurements were correlated to the final
histological findings. RESULTS: The strain rated from 0.01 to 0.84 (mean 0.26 +/- 0.13). A total of 50 thyroid
malignancies (35 papillara carcinoma, 9 medullary carcinoma, and 6 follicular carcinoma) were observed.
Patients (81) were within the hard group, 35 of them (43.2%) had thyroid cancer (TC) in final histology. Out of
132 patients in the intermediate group, 15 patients had TC (11.4%). All 96 patients from the soft group showed
benign histological results (NPV 100%). Seventy percent of patients with TC were within the hard group (PPV
42%). These results were highly significant (p < 0.001). Coarse calcifications and cystic nodules were not
connected with reliable measurements and therefore are not suitable for USE. CONCLUSION: USE is a useful
adjunctive tool in the workup of thyroid nodules. A low strain value needs surgical intervention, whereas a high
strain value predicts a benign histology. It might substitute fine-needle aspiration cytology in the future.
PubMed-ID: 20632029

Diagnostic Utility of Immunohistochemical Panel in Various Thyroid Pathologies.
Langenbecks Arch Surg, 395(7):885-91.
Ozolins A, Narbuts Z, Strumfa I, Volanska G, Gardovskis J. 2010.
BACKGROUND: For management of thyroid nodules, distinction between benign and malignant tumours is
essential. The study was performed to evaluate the diagnostic value of molecular markers in different thyroid
tumours. MATERIALS AND METHODS: Immunohistochemistry for CD56, HBME-1, COX-2, Ki-67, p53 and E-
cadherin (E-CAD) was performed in 113 benign and 35 malignant thyroid lesions including 36 follicular
adenomas (FA), 77 colloid goitres, 26 papillary thyroid carcinomas (PTC) and 9 follicular carcinomas (FC). The
results were scored semiquantitatively by staining intensity (0-3 scale) and percentage of positive cells.
RESULTS: PTC was characterised by decreased E-CAD and CD56 expression in contrast to surrounding
benign thyroid tissues. HBME-1 expression was absent in benign thyroid tissues but was notably high in PTC
and occasionally in FC. The expression of E-CAD and CD56 in FA was significantly higher than in the
surrounding thyroid tissues. No expression of p53 was found in any group. The expression of COX-2 was low in
all lesions. The proliferation activity by Ki-67 was generally low; however, it was significantly higher in cancers.
CONCLUSIONS: The panel consisting of three markers, HBME-1, E-CAD and CD56, can be recommended as
an adjunct to morphology criteria. HBME-1 is found in malignant lesions only and is the most sensitive and
specific single marker in PTC. Decreased expression of E-CAD and CD56 distinguishes PTC from FA and FC.
Both FA and FC are characterised by high expression of E-CAD and CD56. The practical use of Ki-67 is difficult
due to low values. The role of adhesion factors in thyroid malignancies may be superior in comparison with cell
PubMed-ID: 20640858

Impact of Pathognomonic Genetic Alterations on the Prognosis of Papillary Thyroid Carcinoma. ESES
Vienna Presentation.
Langenbecks Arch Surg, 395(7):877-83.
Musholt TJ, Schonefeld S, Schwarz CH, Watzka FM, Musholt PB, Fottner C, Weber MM, Springer E, Schad A.
INTRODUCTION: BRAF mutations and RET or NTRK1 rearrangements were identified as causing events that

ESES Review of Recently Published Literature 2010-3                                                  Page 14 of 68
drive the malignant transformation of the thyroid follicular cell. The impact of these alterations on the course of
papillary thyroid carcinoma (PTC) is still unsettled. PATIENTS AND METHODS: Tumor tissues of 290 (98 male,
192 female) patients were intra-operatively snap frozen or harvested from archival paraffin-embedded blocks
and used for extraction of DNA and RNA. Comprehensive analysis of RET/PTC and NTRK1 rearrangements
was carried out by multiplex screening RT-PCR, hybrid-specific RT-PCR and sequencing of detected hybrids. A
mutation-specific PCR was used for BRAF analysis. RESULTS: The BRAF V600E mutation was detected in
122/290 (42%), RET rearrangements in 20/137 (14.6%), and NTRK1 rearrangements in 15/93 (16.1%) PTCs.
One hundred forty one out of 290 (48.6%) PTCs demonstrated none of the genetic alterations studied. Eight
PTCs expressed two different mutations (1 RET/PTC + BRAF, 6 NTRK1 + BRAF, 1 RET/PTC + NTRK1).
Tumor-specific survival analysis (mean follow-up, 5.5 years) demonstrated no significant difference, but a
tendency toward worse prognosis of BRAF-positive patients compared to BRAF-negative patients or
rearrangement-positive patients, respectively. CONCLUSION: Long-term follow-up data on large tumor panels
are needed to disclose significant survival differences of prognostic predictors on PTC. This study provides
further evidence that patients harboring BRAF-V600E-positive PTCs may experience an unfavorable course of
the disease compared to patients with tumors carrying other genetic alterations.
PubMed-ID: 20640859

Real-Time, High-Resolution Ultrasonography of the Vocal Folds--a Prospective Pilot Study in Patients
Before and After Thyroidectomy.
Langenbecks Arch Surg, 395(7):859-64.
Dedecjus M, Adamczewski Z, Brzezinski J, Lewinski A. 2010.
PURPOSE: The aim of the study was to evaluate the functionality of vocal folds (VF) by real-time, high-
resolution ultrasonography (US) and to correlate the imaged features to results of laryngological examination
(LE). METHODS: The study group comprised 50 patients (41 females and nine males), qualified to
thyroidectomy. All the patients had LE and US examination before and 2 days, 2 months, and 3 months after the
surgery. We used high-resolution US imaging to identify VFs and, subsequently, a pulsed Doppler and Doppler
gate to quantify the tissue displacement velocity in the vibrating VF section. RESULTS: LE revealed unilateral
VF paralysis in two patients. VF dysfunction was diagnosed in other four subjects. In simultaneously performed
US examination, changes in VF displacement velocity (VFDV) were observed in ten patients. In two subjects,
VFDV was below 30 cm/s- patients with VF paralysis, diagnosed in LE. In a further eight cases, we observed
VFDV decrease by 50%, comparing to preoperative values. Both US-imaging and LE, performed after the 3-
month follow-up, confirmed the transitional character of the above-mentioned pathologies. CONCLUSIONS: US
imaging of the VFs correlated with LE results, while being a minimally invasive, easily reproducible, and
inexpensive method of examining VF functionality. Thanks to many recording options, it may soon become a
perfect tool for an early identification of postoperative VF dysfunction with its later monitoring. To our knowledge,
it is the first application of US and Doppler gate modes for VFDF quantification; however, an analysis on a larger
group of patients is necessary to standardize the technique.
PubMed-ID: 20640934

The Accuracy of (18)[F]-Fluoro-2-Deoxy-D-Glucose-Positron Emission Tomography/Computed
Tomography, Ultrasonography, and Enhanced Computed Tomography Alone in the Preoperative
Diagnosis of Cervical Lymph Node Metastasis in Patients With Papillary Thyroid Carcinoma.
World J Surg, 34(11):2564-9.
Morita S, Mizoguchi K, Suzuki M, Iizuka K. 2010.
BACKGROUND: The aim of this study was to evaluate the accuracy of [(18)F]-fluoro-2-deoxy-D: -glucose-
positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography
alone in the preoperative diagnosis of lymph node metastasis in patients with papillary thyroid carcinoma.
METHODS: In a prospective study performed between January 2007 and December 2009, 74 patients with a
diagnosis of papillary thyroid carcinoma confirmed by fine-needle aspiration biopsy were referred to our
institution for surgery. Preoperative assessment of metastasis in the central and lateral cervical lymph nodes
was done using [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography,
ultrasonography, and enhanced computed tomography. The results for each level of cervical node assessed
using these methods were correlated with the pathology reports after surgery. We determined the sensitivity,
specificity, positive and negative predictive values, and diagnostic accuracy of the three methods for all levels of
cervical lymph node. RESULTS: There were no significant differences in the diagnostic results obtained by
[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography and enhanced
computed tomography. However, ultrasonography images gave significantly better results than either [(18)F]-

ESES Review of Recently Published Literature 2010-3                                                   Page 15 of 68
fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography or enhanced computed
tomography alone in identifying metastases on the basis of the level of cervical lymph node. In addition, the
overall diagnostic accuracy tended to be higher for the lateral compartment than for the central compartment.
CONCLUSIONS: Preoperative assessment by ultrasonography of metastases in the central and lateral cervical
lymph nodes might be the best methodology for determining the extent of surgical resection required to remove
metastatic lymph nodes adequately in patients with papillary thyroid carcinoma.
PubMed-ID: 20645089

Surgical Anatomy and Neurophysiology of the Vagus Nerve (VN) for Standardised Intraoperative
Neuromonitoring (IONM) of the Inferior Laryngeal Nerve (ILN) During Thyroidectomy.
Langenbecks Arch Surg, 395(7):893-9.
Dionigi G, Chiang FY, Rausei S, Wu CW, Boni L, Lee KW, Rovera F, Cantone G, Bacuzzi A. 2010.
BACKGROUND: Standardisation of the intraoperative neuromonitoring (IONM) technique is a fundamental
aspect in monitored thyroid surgery. Vagal nerve (VN) stimulation is essential for problem solving, recognition of
any inferior laryngeal nerve (ILN) lesions and prediction of ILN post-operative function. Issues that have been
overlooked in the literature, particularly in terms of prospective approaches, are the topographic relationship of
the VN with the carotid and jugular vessels as well as the neurophysiology of the VN and ILN that have been
studied, with a prospective approach, in patients with various thyroid diseases. METHODS: Cooperation with the
Human Morphology Department resulted in the completion of a dedicated anatomy report, with the clear
objective of providing a detailed anatomic and neurophysiologic description of the VN (n = 263). RESULTS: VN
identification and stimulation was feasible in all cases and did not result in increased morbidity or operative time.
Most VNs lay on the posterior region of the carotid ship (73%), i.e. the P position in accordance with our model.
Mean amplitudes of EMG signals obtained from VN stimulation were 750 +/- 279 muV, lower than those
obtained with direct INL stimulation (1,086 +/- 349 muV). CONCLUSION: A better understanding of the variability
in the VN may be useful not only to minimise complications but also to guarantee an accurate IONM.
PubMed-ID: 20652584

What Are Normal Quantitative Parameters of Intraoperative Neuromonitoring (IONM) in Thyroid Surgery?
Langenbecks Arch Surg, 395(7):901-9.
Lorenz K, Sekulla C, Schelle J, Schmeiss B, Brauckhoff M, Dralle H. 2010.
PURPOSE: This study aimed at definition of normal quantitative parameters in intraoperative neuromonitoring
during thyroid surgery. Only few and single center studies described quantitative data of intraoperative
neuromonitoring. Definition of normal parameters in intraoperative neuromonitoring is believed to be a
prerequisite for interpretation of results and intraoperative findings when using this method. Moreover, these
parameters seem important in regard to the prognostic impact of the method on postoperative vocal cord
function. MATERIAL AND METHODS: In a prospective multicenter study, quantitative analysis of vagal nerve
stimulation pre- and postresection was performed in thyroid lobectomies. A standardized protocol determined set
up and installation of neuromonitoring and defined assessment of quantitative parameters. Data of intraoperative
neuromonitoring were respectively print-documented and centrally analyzed. RESULTS: In six participating
centers a total of 1,289 patients with 1,996 nerves at risk underwent surgery for benign and malignant thyroid
disease. Median amplitude was significantly larger for the right vs. left vagal nerve, latency was significantly
longer for left vs. right vagal nerve and duration of the left vs. right vagal nerve significantly longer. Age
disparities were only present in form of significantly higher amplitude in patients below 40 years; however, there
is no continuous increase with age. Regarding gender, there was significantly higher amplitude and smaller
latency in women compared to men. Duration of surgery revealed a reduction of amplitude with operative time;
contrarily, latency and signal duration remained stable. The type of underlying thyroid disease showed no
influence on quantitative parameters of intraoperative neuromonitoring. CONCLUSIONS: Systematic data of
multicenter evaluation on quantitative intraoperative neuromonitoring parameters revealed differences between
left and right vagal nerves in regard to amplitude, latency and duration of signal, gender, and age. The nature of
thyroid disease showed no significant influence on quantitative parameters of intraoperative neuromonitoring.
This study presents for the first time collective data of a large series of nerves at risk in a multicenter setting. It
seems that definitions of "normal" parameters are prerequisite for the interpretation of quantitative changes of
intraoperative neuromonitoring during thyroid surgery to enable interpretation of influence on surgical strategy
and prediction of postoperative vocal cord function.
PubMed-ID: 20652585

ESES Review of Recently Published Literature 2010-3                                                    Page 16 of 68
Management of Lymph Fistulas in Thyroid Surgery.
Langenbecks Arch Surg, 395(7):911-7.
Lorenz K, Abuazab M, Sekulla C, Nguyen-Thanh P, Brauckhoff M, Dralle H. 2010.
PURPOSE: Postoperative lymphatic leakage following thyroid surgery represents a management problem with
considerate potential morbidity, psychological, and economical impact. Conservative and surgical management
strategies for high- and low-output lymph fistulas are inconsistent. Reliable criteria to predict outcome of
conservative versus surgical treatment in clinically evident lymph fistula are lacking. MATERIAL AND
METHODS: A retrospective single-center chart review of consecutively quality-control-documented thyroid
surgeries from January 1998 to December 2009 was performed to identify reported postoperative lymph fistulas.
Documentation of surgical procedures, drainage, medical, and nutritional management was analyzed to identify
risk factors for occurrence and criteria for management of evident lymph fistulas. RESULTS: There were 29
patients identified with postoperative clinical evidence of lymph fistulas following thyroid surgery; incidence was
0.5%. Indication to surgery comprised benign nodular goiter, recurrent nodular goiter, and thyroid carcinoma or
local and lymphonodal carcinoma recurrences. There were 12 (41%) primary and 17 (59%) redo surgeries
performed. Surgical procedures performed included thyroidectomy, completion thyroidectomy, and primary and
redo central and lateral systematic microdissection of lymphatic compartments. All patients were initially
submitted to fasting diet and medical treatment, successfully in 19 (66%), whereas ten (34%) patients underwent
surgical intervention for fistula closure after failure of conservative treatment. Complications were one wound
infection and fistula recurrence in five (26%) patients in the conservative group and two (20%) in the surgical
group. Hospital stay was exceedingly prolonged in both groups with a median of 21 and 11 versus 6 days in
patients with regular postoperative course following thyroid surgery. CONCLUSIONS: Data of this series support
definition of the two categories of high- and low-output fistulas according to drainage collection with >300 versus
<200 ml/day. Fasting in low-output fistula facilitates conservative treatment with closed drainage, whereas in
high-output fistulas surgical intervention should be sought. Attendant criteria for treatment stratification are
equally important, like patient's compliance, nutritional, and general health status as well as evidence for wound
infection. Surgical closure of lymph fistula may be demanding when identification of the secreting fistula is limited
and even muscle flap fortification may fail. Ultimately, in unsuccessfully reoperated fistula recurrences, open
drainage may become necessary. Lymph fistulas cause significantly prolonged hospital stay, possible critical
clinical decay, and unfavorable cosmetic and oncologic outcome while the superior management remains to be
PubMed-ID: 20652586

Is Fine-Needle Aspiration Cytology for Thyroid Nodules a Routine and Safe Procedure? A Series of
Emergency Cervicotomies Following FNAC.
Langenbecks Arch Surg, 395(7):873-6.
Donatini G, Masoni T. 2010.
PURPOSE: Fine-needle aspiration cytology (FNAC) is a widely used diagnostic tool to assess thyroid lesions,
with a low morbidity rate. Although neck hematomas following FNAC are reported, only four cases of massive
hemorrage resulting in acute airways obstruction have been previously described. METHODS: We report a
series of three emergency cervicotomies for a massive neck hematoma causing acute respiratory distress after a
thyroid FNAC. RESULTS: Endotracheal intubation followed by decompressive cervicotomy and surgical neck
exploration was made in all patients. Two patients underwent isthmectomy, while a left thyroid lobectomy plus
left lateral neck lymphadenectomy was performed in the third case. Extubation was achieved within 12 h in the
ICU. All patients were discharged uneventfully within 72 h. CONCLUSIONS: Acute thyroid hemorrage is a very
rare but possible complication of FNAC, potentially fatal for the patient. Prompt evaluation and intervention is
mandatory for patients with rapidly evolving symptoms.
PubMed-ID: 20652588

Detection of Papillary Thyroid Carcinoma by Analysis of BRAF and RET/PTC1 Mutations in Fine-Needle
Aspiration Biopsies of Thyroid Nodules.
World J Surg, 34(11):2595-603.
Musholt TJ, Fottner C, Weber MM, Eichhorn W, Pohlenz J, Musholt PB, Springer E, Schad A. 2010.
BACKGROUND: Activating mutations of the oncogene BRAF or rearrangements of the tyrosine kinase receptor
RET are observed in up to 80% of papillary thyroid carcinomas (PTCs). The predominant BRAF V600E mutation
has not been detected in benign thyroid tissue so far, so consequently, this assumedly pathognomonic alteration
is qualified to improve the preoperative diagnosis of PTC. METHODS: Two hundred ninety preoperatively
harvested fine-needle aspiration biopsies (FNABs) underwent routine cytologic assessment. BRAF V600E

ESES Review of Recently Published Literature 2010-3                                                  Page 17 of 68
mutation analysis was performed by mutation-specific PCR using the same cell material; a hybrid-specific RT-
PCR assay was used for detection of RET/PTC1 rearrangements. Detected genetic alterations were verified by
direct sequencing. Definitive histopathology was obtained in 93/290 lesions following surgery of the respective
thyroid nodule. RESULTS: While cytology alone diagnosed 13/30 malignancies (22 PTCs, 4 FTCs, 1 MTC, 1
UTC, 2 metastases), five additional malignancies were identified by supplementary mutation analysis. Cytology
classified eight FNABs as benign, while postoperative histology demonstrated a thyroid malignancy (6 PTCs, 1
FTC, 1 metastasis). In four of these eight cases, the genetic analysis detected a BRAF V600E mutation or a
RET/PTC1 rearrangement. Classifying both suspicious and malignant FNAB results as positive cytology results,
supplementary genetic testing increased the overall sensitivity of FNAB from 70.4 to 85.7%, the positive
predictive value (PPV) from 59.4 to 64.9%, and the negative predictive value (NPV) from 84.0 to 91.3%.
CONCLUSIONS: Supplementary mutation analysis of RET and especially of the BRAF V600E mutation in
FNABs is a fast and probably cost-effective assay in routine diagnostic setting. Mutation analyses of PTC-
specific genetic alterations improve the preoperative identification and prognostic assessment of thyroid
malignancies and therefore enable an optimized surgical strategy.
PubMed-ID: 20652698

Identification and Optimal Postsurgical Follow-Up of Patients With Very Low-Risk Papillary Thyroid
J Clin Endocrinol Metab, 95(11):4882-8.
Durante C, Attard M, Torlontano M, Ronga G, Monzani F, Costante G, Ferdeghini M, Tumino S, Meringolo D,
Bruno R, De TG, Crocetti U, Montesano T, Dardano A, Lamartina L, Maniglia A, Giacomelli L, Filetti S. 2010.
CONTEXT: Most papillary thyroid microcarcinomas (PTMCs; </= 1 cm diameter) are indolent low-risk tumors,
but some cases behave more aggressively. Controversies have thus arisen over the optimum postoperative
surveillance of PTMC patients. OBJECTIVES: We tested the hypothesis that clinical criteria could be used to
identify PTMC patients with very low mortality/recurrence risks and attempted to define the best strategy for their
management and long-term surveillance. DESIGN: We retrospectively analyzed data from 312 consecutively
diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-
neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional
inclusion criteria were complete follow-up data from surgery to at least 5 yr after diagnosis. All 312 had
undergone (near) total thyroidectomy [with radioactive iodine (RAI) remnant ablation in 137 (44%) - RAI group]
and were followed up yearly with cervical ultrasonography and serum thyroglobulin, TSH, and thyroglobulin
antibody assays. RESULTS: During follow-up (5-23 yr, median 6.7 yr), there were no deaths due to thyroid
cancer or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were
negative in all cases. Final serum thyroglobulin levels were undetectable (<1 ng/ml) in all RAI patients and
almost all (93%) of non-RAI patients. CONCLUSION: Accurate risk stratification can allow safe follow-up of most
PTMC patients with a less intensive, more cost-effective protocol. Cervical ultrasonography is the mainstay of
this protocol, and negative findings at the first postoperative examination are highly predictive of positive
PubMed-ID: 20660054

Familial Nonmedullary Thyroid Carcinoma-Clinical Relevance and Prognosis. A European Multicenter
Study. ESES Vienna Presentation.
Langenbecks Arch Surg, 395(7):851-8.
Hillenbrand A, Varhaug JE, Brauckhoff M, Pandev R, Haufe S, Dotzenrath C, Koberle R, Hoffmann R, Klein G,
Kadmon M, Negele T, Hagieva T, Henne-Bruns D, Luster M, Weber T. 2010.
PURPOSE: Approximately 5% of differentiated thyroid carcinomas are of familial origin. These familial
nonmedullary thyroid carcinomas (FNMTC) have an increased risk of multifocal disease and lymph node
involvement. Consequently, higher recurrence rates and decreased disease-specific survival rates are
described. The best surgical approach is discussed controversially. PATIENTS AND METHODS: A survey
among the international members of the German Society of Endocrine Surgeons revealed 20 families with two or
more first-degree relatives with FNMTC. The mean age of the 41 patients (30 female, 11 male) with FNMTC was
40.6 years (18-73 years). RESULTS: Total thyroidectomy was performed in 31 of 41 patients (76%). Ninety-five
percent of the tumors were papillary carcinomas. Two of 41 patients had follicular carcinomas. Ten patients
(24%) with papillary carcinomas were diagnosed with Hashimoto's thyroiditis. The mean tumor size was 1.45
cm. FNMTC was multifocal in 12 patients (29%). A systematic lymph node dissection was performed in 21 of 41
patients (51%). Lymph nodes metastases were found in seven of these 21 patients. Twenty-eight of the patients
(68%) underwent postoperative radioiodine ablation. After a mean follow-up of 7.2 years, 39 patients (95%) were

ESES Review of Recently Published Literature 2010-3                                                 Page 18 of 68
disease free. One patient developed local recurrence and lung metastases, 10 and 25 years, respectively, after
initial diagnosis. Another patient died 2 years postoperatively from advanced metastatic disease.
CONCLUSIONS: FNMTC is associated with an early onset of small, mostly papillary thyroid carcinomas and an
increased risk of multifocality and lymph node involvement. Total thyroidectomy and systematic neck dissection
are recommended together with radioiodine ablation. Screening for first-degree relatives should start at age 18
PubMed-ID: 20683623

Clinical Implication of the Number of Central Lymph Node Metastasis in Papillary Thyroid Carcinoma:
Preliminary Report.
 World J Surg, 34(11):2558-63.
Lee YS, Lim YS, Lee JC, Wang SG, Kim IJ, Lee BJ. 2010.
BACKGROUND: Papillary thyroid cancer (PTC) metastasizes to central lymph node (CLN). CLN metastasis is
associated with high risk of locoregional recurrence and distant metastasis. The significance of the number of
metastatic CLN has not been addressed. This study was designed to evaluate the clinical implication of the
number of metastatic CLN in PTC. METHODS: We reviewed the patients who underwent total thyroidectomy
and CLN dissection with or without lateral neck dissection due to PTC, from March 2008 to June 2009. The
relationships between the number of CLN and risk factors, including age, gender, tumor size, extrathyroidal
extension, and lateral lymph node metastasis, were assessed. Patients were divided into three groups according
to the number of CLN: group A = 0; group B = 1-2; and group C = >/=3. RESULTS: Of 258 patients enrolled in
this study, 113 were in group A, 73 in group B, and 72 in group C. Extrathyroidal extension and lateral neck
lymph node metastasis were related to increased rate of CLN metastasis (P < 0.05). Tumor size increased as
the number of CLN increased; group C had the largest tumor size (P < 0.05). When evaluating the distribution of
patients with extrathyroidal extension, group C had a significant odds ratio (4.213, P < 0.05). When evaluating
the distribution of lateral neck lymph node metastasis, groups B and C had significant odds ratio (14.353,
75.403, respectively, P < 0.05). CONCLUSIONS: The number of CLN metastasis correlated with the negative
prognostic factors, including tumor size, extrathyroidal extension, and lateral neck lymph node metastasis. This
suggests that the number of CLN has prognostic implication.
PubMed-ID: 20703463

Prognostic Significance of Ki-67 Labeling Index in Papillary Thyroid Carcinoma.
World J Surg, 34(12):3015-21.
Ito Y, Miyauchi A, Kakudo K, Hirokawa M, Kobayashi K, Miya A. 2010.
BACKGROUND: Ki-67 is a useful tool for evaluating cell proliferative activity in various tumors. Although the
utility of Ki-67 labeling index (LI) to diagnose thyroid neoplasms has been investigated, little is known regarding
the relationship between Ki-67 LI and the biological behavior of papillary thyroid carcinoma. In this study, we
examined Ki-67 in 371 patients with papillary thyroid carcinoma to elucidate this issue. METHODS: A total of 371
patients with papillary carcinoma who underwent initial and locally curative surgery between 1996 and 1997
were enrolled in this study. We immunohistochemically investigated Ki-67 LI in their primary lesions and
compared this finding with various clinicopathological features, including patient prognosis. RESULTS: Ki-67 LI
was </=1% in 213 patients (57%) and among the remaining 158, 35 showed Ki-67 LI >3%. Ki-67 LI was
associated with patient age, massive extrathyroid extension, and distant metastasis at surgery. Of 363 patients
without distant metastasis at surgery, 54 (15%) showed carcinoma recurrence during follow-up (average 124
months) and the disease-free survival (DFS) of patients with Ki-67 LI >1% was significantly worse than that of
those with Ki-67 LI <1% (p < 0.0001). On multivariate analysis, Ki-67 LI was recognized as an independent
prognostic factor for the DFS of patients. Although only eight patients died of carcinoma in our series, patients
with Ki-67 LI >3% showed a significantly worse cause-specific survival (CSS) than those with Ki-67 LI <3% (p <
0.0001). CONCLUSIONS: Careful evaluation of Ki-67 LI in primary lesions can predict DFS and CSS of patients
with papillary thyroid carcinoma.
PubMed-ID: 20703465

Molecular Testing for Somatic Mutations Improves the Accuracy of Thyroid Fine-Needle Aspiration
World J Surg, 34(11):2589-94.
Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH, Kebebew E. 2010.
BACKGROUND: Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of

ESES Review of Recently Published Literature 2010-3                                                Page 19 of 68
cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on
histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To
determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial.
METHODS: Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for
common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS,
TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were
determined based on the histologic diagnosis. RESULTS: One hundred twenty-five of 455 thyroid nodule FNA
biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23
BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more
mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were
indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of
65%. CONCLUSIONS: Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and
identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic
testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those
with positive results.
PubMed-ID: 20703476

Outcome of Protracted Hypoparathyroidism After Total Thyroidectomy.
Br J Surg, 97(11):1687-95.
Sitges-Serra A, Ruiz S, Girvent M, Manjon H, Duenas JP, Sancho JJ. 2010.
BACKGROUND: Although the variables that influence the development of post-thyroidectomy hypocalcaemia
are now better understood, the risk factors and long-term outcome of persistent hypoparathyroidism (HPP) are
poorly defined. A retrospective review of a prospective protocol for the management of post-thyroidectomy
hypocalcaemia was performed. METHODS: Patients with a serum calcium level below 8 mg/dl (2 mmol/l) 24 h
after total thyroidectomy were prescribed oral calcium with or without calcitriol and followed for at least 1 year.
Protracted HPP was defined as an intact parathyroid hormone (iPTH) level below 13 pg/ml and need for calcium
medication at 1 month after thyroidectomy. RESULTS: Of 442 patients (343 with goitre, 99 with carcinoma)
undergoing total thyroidectomy, 222 (50.2 per cent) developed postoperative hypocalcaemia. Eleven patients
were lost to follow-up. Parathyroid function recovered in 131 patients within 1 month and 80 developed
protracted HPP, which was associated with lymphadenectomy, fewer than three glands left in situ and incidental
parathyroidectomy. Parathyroid function recovered within 1 year in 78 per cent of patients with protracted HPP.
Factors associated with late recovery of parathyroid function were higher serum calcium and low but detectable
iPTH levels 1 month after surgery. These factors were associated with higher calcitriol and calcium dosages at
hospital discharge. Parathyroid autotransplantation did not protect against permanent HPP. CONCLUSION:
Higher serum calcium levels at 1 month after total thyroidectomy are associated with recovery of parathyroid
function. It is hypothesized that intensive medical treatment of hypocalcaemia-'parathyroid splinting'-may
improve the outcome of patients with protracted HPP.
PubMed-ID: 20730856

The RET Polymorphic Allele S836S Is Associated With Early Metastatic Disease in Patients With
Hereditary or Sporadic Medullary Thyroid Carcinoma.
Endocr Relat Cancer, 17(4):953-63.
Siqueira DR, Romitti M, da Rocha AP, Ceolin L, Meotti C, Estivalet A, Punales MK, Maia AL. 2010.
The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a
matter of debate. Here, we investigate whether the RET variants L769L, S836S, and G691S/S904S influence
disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC
and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET
polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No
associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism,
lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those
without this allele (17+/-8.2 vs 28.6+/-14.4 years, P=0.01), suggesting that these patients had metastases at a
young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan-
Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S
variant (P=0.003 and P=0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients
than in controls (10.5 vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6+/-13.3 vs
48.5+/-16.7 years, P=0.02) and showed a higher percentage of lymph node and distant metastases (P=0.02 and

ESES Review of Recently Published Literature 2010-3                                                 Page 20 of 68
P=0.04 respectively). Kaplan-Meier estimates of lymph node and distant metastases yielded distinct curves for
patients with or without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses using a COX
regression model showed that the S836S variant was independently associated with metastatic disease (hazard
ratio 2.82 (95% confidence interval 1.51-5.26), P=0.001). In conclusion, the RET S836S variant is associated
with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.
PubMed-ID: 20801952

Real-Time Elastosonography: Useful Tool for Refining the Presurgical Diagnosis in Thyroid Nodules
With Indeterminate or Nondiagnostic Cytology.
J Clin Endocrinol Metab, 95(12):5274-80.
Rago T, Scutari M, Santini F, Loiacono V, Piaggi P, Di CG, Basolo F, Berti P, Pinchera A, Vitti P. 2010.
BACKGROUND: Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle
aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of
malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to
differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE
in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology. PATIENTS: The study
included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic
cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142
indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate),
or 3 (low). RESULTS: In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of
benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining
the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic
cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By
combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%. CONCLUSIONS: USE
may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or
nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.
PubMed-ID: 20810572

Does Routine Use of Ultrasound Result in Additional Thyroid Procedures in Patients With Primary
J Am Coll Surg, 211(4):536-9.
Adler JT, Chen H, Schaefer S, Sippel RS. 2010.
BACKGROUND: Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate
preoperative imaging. Cervical ultrasound is commonly used to localize parathyroid adenomas, but can lead to
discovery of concomitant thyroid gland pathology requiring modification of the operative approach. How the
identification of incidental thyroid lesions affects patient management is unclear. STUDY DESIGN: A prospective
database of patients undergoing parathyroidectomy was analyzed for thyroid pathology discovered by
ultrasound. Lesions were biopsied if indicated, and operative management was adjusted accordingly. Clinical
data were correlated with operative decision-making. RESULTS: Between July 2002 and November 2009, 310
patients with primary hyperparathyroidism underwent ultrasound. Concomitant thyroid pathology was noted in 89
(29%) patients. Thirty-seven patients (42% of pathology) underwent fine-needle aspiration of a thyroid nodule.
Thirteen patients (4% of all patients) underwent a thyroid operation not related to parathyroid disease: 9 thyroid
lobectomies for presumably benign nodules and 4 total thyroidectomies for malignancy. Two were for confirmed
papillary thyroid cancer, and the other 2 were for an indeterminate biopsy that later proved to be papillary thyroid
cancer. One lobectomy discovered microscopic papillary thyroid cancer independent of the biopsied nodule. In
total, 5 (2% of all patients) malignancies were discovered. CONCLUSIONS: Twenty-nine percent of patients with
primary hyperparathyroidism had concomitant thyroid pathology on ultrasound. Forty-two percent of these
patients underwent biopsy, and 2% had malignant pathology. Routine use of ultrasound in patients with primary
hyperparathyroidism leads to discovery of unrecognized thyroid pathology and cancer.
PubMed-ID: 20822743

Prognostic Impact of Extrathyroid Extension and Clinical Lymph Node Metastasis in Papillary Thyroid
Carcinoma Depend on Carcinoma Size.
World J Surg, 34(12):3007-14.
Fukushima M, Ito Y, Hirokawa M, Miya A, Shimizu K, Miyauchi A. 2010.
BACKGROUND: Although papillary thyroid carcinoma (PTC) generally has an indolent nature, massive

ESES Review of Recently Published Literature 2010-3                                                  Page 21 of 68
extrathyroid extension (Ex) and clinical lateral node metastasis (N1b) are prominent predictors of a dire
prognosis. However, it remains unknown whether these factors affect patient prognosis with uniformity. In this
study, we investigated the relationships between the prognostic impact of these factors and carcinoma size.
METHODS: A total of 5,917 patients who underwent initial and curative surgery for PTC between 1987 and 1995
were enrolled in this study. After dividing these patients into four subsets based on tumor size--<==1.0 cm, 1.1-
2.0 cm, 2.1-3.0 cm, and >3.0 cm--we investigated the prognostic impacts of Ex and N1b in each subset.
RESULTS: Relative risk (RR) of disease-free survival (DFS) of N1b was the highest in the subset <==1.0 cm
and decreased with tumor size. RR of Ex was smaller in carcinoma <==3.0 cm but larger in carcinoma >3.0 cm
compared with that of N1b in the respective subsets. On multivariate analysis, N1b was a more important
prognostic factor than Ex in carcinoma <==3.0 cm, but the prognostic impacts of these two factors were reversed
in carcinoma >3.0 cm. Similar findings were obtained in analyses for cause-specific survival (CSS) and
prognostic value of N1b was more significant in carcinoma <==3.0 cm but less significant in carcinoma >3.0 cm
than that of Ex. CONCLUSIONS: The prognostic values of Ex and N1b vary with tumor size in PTC. It is
important for physicians to pay attention to tumor size when evaluating the prognostic impact of these two
prominent factors.
PubMed-ID: 20824274

Invisible Scar Endoscopic Dorsal Approach Thyroidectomy: a Clinical Feasibility Study.
World J Surg, 34(12):2997-3006.
Schardey HM, Barone M, Portl S, von AM, von AT, Schopf S. 2010.
BACKGROUND: The aim of the present study was to test the safety and feasibility of the dorsal approach
endoscopic thyroidectomy procedure in a prospective trial in humans, after the procedure had been developed
ex vivo in human cadavers. METHODS: A total of 28 patients were enrolled for 30 unilateral procedures of
thyroidectomy. Two cases were staged bilateral procedures. Patients presenting with suspicious cold nodules,
hot nodules, or goiters were operated on under general anaesthesia. Skin incision is carried out on the scalp,
behind the ear. Deep to the sternocleidomastoid muscle, but respecting the superficial cervical fascia, the
preparation goes past the carotid triangle to reach the thyroid below the straight neck muscles. Postoperatively
the patients underwent neurological assessment, vocal cord examination, clinical control for hemorrhage, and
determination of serum levels of Ca(2+). RESULTS: Thirty unilateral procedures by the dorsal approach were
carried out in 22 women and 6 men. There was 1 subtotal thyroidectomy and 29 total unilateral thyroidectomies
with no conversions. There was one permanent recurrent laryngeal nerve (RLN) lesion and one postoperative
hemorrhage. The size of the lobes removed ranged from 6 to 40 ml (mean: 18 ml). In four cases the specimen
exceeded 38 ml. There was one multifocal papillary cancer requiring open surgical revision and
lymphadenectomy. The other diagnoses were benign. All wounds healed by primary intention. Temporary
impairment of cervical nerves was detected in six patients. It was possible to avoid access-related problems by
improving the patient's positioning on the operating table, omitting straight instruments, and respecting the
superficial fascia before entering the carotid triangle. CONCLUSIONS: Hemithyroidectomy by the dorsal
approach is feasible. It is a single surgeon, single port, gasless unilateral endoscopic technique with the option
to go bilateral.
PubMed-ID: 20835708

Follicular Variant of Papillary Thyroid Carcinoma Presenting As a Toxic Nodule by I-123 Scintigraphy.
Clin Nucl Med, 35(10):770-5.
Bommireddipalli S, Goel S, Gadiraju R, Paniz-MondolFi A, DePuey EG. 2010.
The risk of malignancy in a "hot" thyroid nodule detected by radioiodine scintigraphy is rare. We report a case of
a 63-year-old man with a hyperfunctioning nodule demonstrated by radioiodine scintigraphy and cytology
suspicious for follicular variant of papillary thyroid carcinoma (FVPTC). There were no locoregional or distant
metastases at initial diagnosis. Histopathologic examination following thyroidectomy confirmed the presence of
an encapsulated FVPTC. A year into follow-up, his I-131 whole body scan performed following the withdrawal
from exogenous thyroid hormone was negative, whereas his serum thyroglobulin (Tg) levels were intermediate.
A subsequent PET/CT scan revealed a small, but stable, metabolically active pretracheal lymph node, which on
biopsy was confirmed to be stage III FVPTC. In conclusion, the presence of hyperfunctioning thyroid nodule(s)
does not preclude malignancy and, therefore, proper cytohistologic evaluation in such patients may help to
exclude a coexistent thyroid carcinoma. Patients treated for localized PTC may benefit from serial PET/CT
follow-up in the early detection and management of recurrence or distant metastases.
PubMed-ID: 20838284

ESES Review of Recently Published Literature 2010-3                                                 Page 22 of 68
Thyroid Cancer Recurrence in Patients Clinically Free of Disease With Undetectable or Very Low Serum
Thyroglobulin Values.
J Clin Endocrinol Metab, 95(12):5241-8.
Kloos RT. 2010.
DESIGN: This was a retrospective clinical study. SETTING: The study was conducted at a university-based
tertiary cancer hospital. PATIENTS: One hundred seven patients had initial thyroid cancer surgery and
subsequent remnant radioiodine ablation. Patients underwent recombinant human TSH (rhTSH)-mediated
diagnostic whole-body scan and rhTSH-stimulated thyroglobulin (Tg) measurement before April 2001 if they had
no antithyroglobulin antibodies, were clinically free of disease, and had one or more undetectable (</=0.5 ng/ml)
or low (0.6-1 ng/ml) basal Tg measurements on levothyroxine. Patients were stratified according to their rhTSH-
Tg responses: group 1, Tg 0.5 ng/ml or less (68 patients); group 2, Tg from 0.6 to 2.0 ng/ml (19 patients); and
group 3, Tg greater than 2 ng/ml (20 patients). MAIN OUTCOME MEASURES: Tumor recurrence was
measured. RESULTS: In group 1, two of 62 patients (3%) with follow-up recurred. In group 2, 63% converted to
group 1, whereas two of 19 (11%) converted to group 3 and then recurred. Sixteen of the initial 20 group 3
patients (80%) recurred, including recurrence rates of 69 and 100% for those with an initial rhTSH-Tg greater
than 2.0 ng/ml but 5.0 ng/ml or less, and 4.6 ng/ml or greater, respectively. One group 3 patient died of distant
metastases. rhTSH-Tg more accurately predicted tumor recurrence than basal Tg. An rhTSH-Tg threshold of 2.5
ng/ml or greater optimally predicted future recurrence with sensitivity, specificity, and negative and positive
predictive values of 80, 97, 95, and 84%, respectively. CONCLUSIONS: The prevalence of postablation thyroid
cancer recurrence is predicted by the rhTSH-Tg response with an optimal Tg threshold of 2.5 ng/ml. Still,
recurrent disease occurs in some patients with an initial rhTSH-Tg of 0.5 ng/ml or less.
PubMed-ID: 20843945

Diminishing Diagnosis of Follicular Thyroid Carcinoma.
Head Neck, 32(12):1629-34.
Otto KJ, Lam JS, MacMillan C, Freeman JL. 2010.
BACKGROUND: Follicular carcinomas have been reported as 10% to 15% of thyroid malignancies. Refinements
in the histologic criteria applied in the classification of follicular lesions have occurred. We aim to document the
true incidence of follicular cancers in a cohort from a high-volume endocrine practice. METHODS: Patient charts
were reviewed and cancers were classified into major subtypes; papillary cancers were further classified by
common variants. Proportions were compared to historic Surveillance, Epidemiology, and End Results (SEER)
database proportions. RESULTS: Only 2.7% of patients had follicular carcinoma. The proportion of patients with
follicular cancer was less than the reported rates of 10% to 15%, and less than the 6.7% extrapolated from
SEER. CONCLUSION: The proportion of follicular cancers is less than traditionally reported. This change is due
to an increased incidence of papillary cancers, and modifications of the histologic criteria used for classification
of encapsulated follicular lesions. There are potential prognostic consequences, as follicular cancers have been
perceived as more aggressive.
PubMed-ID: 20848402

Thyroid Surgery With the New Harmonic Scalpel: A Prospective Randomized Study.
Surgery, 149(3):411-5.
Markogiannakis H, Kekis PB, Memos N, Alevizos L, Tsamis D, Michalopoulos NV, Lagoudianakis EE, Toutouzas
KG, Manouras A. 2011.
BACKGROUND: Despite their safety and effectiveness in thyroid surgery, the previous harmonic scalpel
instruments are considered large and cumbersome by several surgeons. An innovative technical improvement of
the device has been made available since 2008. The objective of this study was to compare the results of total
thyroidectomy using the new harmonic scalpel (FOCUS) with that with the previously available device
(HARMONIC ACE). METHODS: A prospective randomized study of all total thyroidectomies between February
and July 2008 was conducted. Patients (n = 90) were randomized to undergo total thyroidectomy with FOCUS
(group A, n = 45) or HARMONIC ACE (group B, n = 45). RESULTS: No significant differences were identified
between the 2 groups in terms of demographics, reoperative thyroid surgery, thyroid gland weight and diameter,
pathologic diagnosis, preoperative and postoperative serum PTH and calcium levels, postoperative
complications, duration of hospital stay, and final outcome. The mean operative time was less in group A than
group B (63 +/- 7 min vs 76 +/- 8 min, P = .009). CONCLUSION: The new harmonic scalpel is a useful adjunct to
the armamentarium of the thyroid surgeon. It is safe, effective, and hand friendly, offering great capabilities for
delicate tissue grasping and dissection. Use of this device decreased operative time compared with the
previously available instrument.

ESES Review of Recently Published Literature 2010-3                                                 Page 23 of 68
PubMed-ID: 20850853

Relationship Between Thyroid Stimulating Hormone and Thyroid Stimulating Immunoglobulin in Graves'
J Endocrinol Invest,
Woeber KA. 2010.
Background and Aim: In Graves' hyperthyroidism suppression of serum TSH after restoration of normal serum
T4 and T3 with treatment has been attributed to binding of TSH-receptor antibodies to TSH receptors in the
pituitary. Accordingly, the relationship between TSH and serum thyroid stimulating immunoglobulin (TSI) was
examined during follow-up of patients with Graves' hyperthyroidism. Subjects and Methods: 23 patients with
Graves' hyperthyroidism were identified who met the inclusion criteria of at least 24 months follow-up after
initiation of methimazole and availability of concurrent measurements of serum TSH and TSI. Results: TSI
disappeared in 12 patients (Group A) and persisted in 11 patients (Group B). Initial T4 was not significantly
different between the 2 groups. However, TSI was significantly lower in Group A than Group B [median
(interquartile range) 179 (152-212) % vs.255 (208-369) %, p=0.0009]. In Group A, TSH normalized during
treatment, and this anteceded disappearance of TSI by a significant time interval [median (interquartile range) 6
(3-8) months vs. 15 (11-20) months, p=0.005]. In Group B, TSI persisted in all patients during follow-up ranging
from 24 to 73 months. No correlation was found to exist between serum TSH and TSI, and for Group B TSI at
final follow-up was not significantly different from the initial value [median (interquartile range) 255 (208-369) %
vs. 236 (160-310) %, p=0.4]. Conclusions: These findings do not support the suggestion that TSI has a direct
suppressive effect on TSH secretion.
PubMed-ID: 20855936

Outcomes of Children and Adolescents With Well-Differentiated Thyroid Carcinoma and Pulmonary
Metastases Following (1)(3)(1)I Treatment: a Systematic Review.
Thyroid, 20(10):1095-101.
Pawelczak M, David R, Franklin B, Kessler M, Lam L, Shah B. 2010.
BACKGROUND: The optimal dose and efficacy of (1)(3)(1)I treatment of children and adolescents with well-
differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic
challenge is to achieve the maximum benefit of (1)(3)(1)I to decrease disease-related morbidity and obtain
disease-free survival while avoiding the potential complications of (1)(3)(1)I therapy. SUMMARY: We
systematically reviewed the published literature on children and adolescents with WDTC and pulmonary
metastases treated with (1)(3)(1)I to examine outcomes after (1)(3)(1)I administration and the risks and benefits
of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric
and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis
spanning a follow-up period of 0.6-45 years. (1)(3)(1)I therapy after surgery and thyrotropin suppression resulted
in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five
studies provided data on disease response in relation to (1)(3)(1)I dose. In general, nonresponders received the
highest (1)(3)(1)I doses and complete responders received a higher dose than partial responders. The disease-
specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient.
One out of 11 patients studied experienced radiation fibrosis. CONCLUSIONS: This review confirms that the
majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with (1)(3)(1)I do not
achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is
therefore prudent to use caution in the repeated administration of (1)(3)(1)I to such patients to ensure that
adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural
course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality,
recurrence rate, dose-specific response, and dose-related adverse effects of (1)(3)(1)I in this patient population.
PubMed-ID: 20860418

Dietary Iodine Restriction in Preparation for Radioactive Iodine Treatment or Scanning in Well-
Differentiated Thyroid Cancer: a Systematic Review.
Thyroid, 20(10):1129-38.
Sawka AM, Ibrahim-Zada I, Galacgac P, Tsang RW, Brierley JD, Ezzat S, Goldstein DP. 2010.
BACKGROUND: Dietary iodine is often restricted before radioactive iodine (RAI) scanning or treatment of well-
differentiated thyroid cancer. Our objective was to examine the impact of a low-iodine diet (LID) before RAI
treatment or scanning on the following outcomes: (i) the efficacy of thyroid remnant ablation (or residual disease

ESES Review of Recently Published Literature 2010-3                                                  Page 24 of 68
elimination), (ii) urinary iodine measurements, (iii) RAI kinetics, and (iv) long-term thyroid cancer outcomes.
METHODS: We performed a systematic review of the English literature. We searched four electronic databases
and conducted a hand search. Two reviewers independently screened citations and reviewed full-text articles
and reached consensus on included articles. Two reviewers independently abstracted data. RESULTS: We
reviewed 76 abstracts or citations and 26 full-text articles. Eight studies were included in the review. The most
commonly studied diets allowed </= 50 microg/day of iodine for 1-2 weeks. In one study, 6-month successful
remnant ablation rates were higher in patients following an LID than in controls. However, in another study, there
was no significant benefit of an LID. LIDs reduce urinary iodine measurements and appear to increase I-131
uptake or lesional radiation compared to regular diets. No studies have examined long-term recurrence or
mortality rates. CONCLUSIONS: Given that LIDs reduce urinary iodine measurements, increase I-131 uptake,
and possibly improve efficacy of I-131 treatment, we currently favor the use of a 1-2-week LID before I-131
therapy or scanning. However, more research is needed to clarify the role of this dietary intervention.
PubMed-ID: 20860420

Impact of Pregnancy on Outcome and Prognosis of Survivors of Papillary Thyroid Cancer.
Thyroid, 20(10):1179-85.
Hirsch D, Levy S, Tsvetov G, Weinstein R, Lifshitz A, Singer J, Shraga-Slutzky I, Grozinski-Glasberg S, Shimon
I, Benbassat C. 2010.
BACKGROUND: Papillary thyroid cancer (PTC) commonly affects women of child-bearing age. During normal
pregnancy, several factors may have a stimulatory effect on normal and nodular thyroid growth. The aim of the
study was to determine whether pregnancy in thyroid-cancer survivors poses a risk of progression or recurrence
of the disease. METHODS: The files of 63 consecutive women who were followed at the Endocrine Institute for
PTC in 1992-2009 and had given birth at least once after receiving treatment were reviewed for clinical,
biochemical, and imaging data. Thyroglobulin levels and neck ultrasound findings were compared before and
after pregnancy. Demographic and disease-related characteristics and levels of thyroid-stimulating hormone
(TSH) during pregnancy were correlated with disease persistence before conception and disease progression
during pregnancy using Pearson's analysis. RESULTS: Mean time to the first delivery after completion of
thyroid-cancer treatment was 5.08 +/- 4.39 years; mean duration of follow up after the first delivery was 4.84 +/-
3.80 years. Twenty-three women had more than one pregnancy, for a total of 90 births. Six women had evidence
of thyroid cancer progression during the first pregnancy; one of them also showed disease progression during a
second pregnancy. Another two patients had evidence of disease progression only during their second
pregnancy. Mean TSH level during pregnancy was 2.65 +/- 4.14 mIU/L. There was no correlation of disease
progression during pregnancy with pathological staging, interval from diagnosis to pregnancy, TSH level during
pregnancy, or thyroglobulin level before conception. There was a positive correlation of cancer progression with
persistence of thyroid cancer before pregnancy and before total I-131 dose was administered. CONCLUSIONS:
Pregnancy does not cause thyroid cancer recurrence in PTC survivors who have no structural or biochemical
evidence of disease persistence at the time of conception. However, in the presence of such evidence, disease
progression may occur during pregnancy, yet not necessarily as a consequence of pregnancy. The finding that a
nonsuppressed TSH level during pregnancy does not stimulate disease progression suggests that it may be an
acceptable therapeutic goal in this setting.
PubMed-ID: 20860423

Molecular, Morphologic, and Outcome Analysis of Thyroid Carcinomas According to Degree of
Extrathyroid Extension.
Thyroid, 20(10):1085-93.
Rivera M, Ricarte-Filho J, Tuttle RM, Ganly I, Shaha A, Knauf J, Fagin J, Ghossein R. 2010.
BACKGROUND: The impact of varying degrees of extrathyroid extension (ETE), especially microscopic ETE
(METE), on survival in thyroid carcinomas (TC) has not been well established. Our objective was to analyze ETE
at the molecular and histologic levels and assess the effect of its extent on outcome. METHODS: All cases of TC
with ETE but without nodal metastases at presentation (NMP) were identified over a 20-year period and grouped
into gross and METE. Twelve papillary thyroid carcinomas (PTCs) without ETE and NMP were also analyzed.
Cases with paraffin tissues were subjected to mass spectrometry genotyping encompassing the most significant
oncogenes in TC: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, and AKT1, and other related
genes were surveyed. RESULTS: Eighty-one (10%) of 829 patients in the database had ETE and no NMP.
There was a much higher frequency of poorly differentiated and anaplastic carcinomas (12/29, 41%) in patients
with gross ETE than in those with METE (3/52, 6%) (p < 0.01). There was a higher disease-specific survival
(DSS) in patients with METE than in those with gross ETE (p < 0.0001). Except for an anaplastic case, no

ESES Review of Recently Published Literature 2010-3                                                Page 25 of 68
recurrences were detected in 45 patients with METE, including 23 PTC patients followed up for a median of 10
years without radioactive iodine therapy. Within patients with gross invasion into trachea/esophagus, tumors with
high mitotic activity and/or tumor necrosis correlated with worse DSS (p < 0.05). Fifty-six cases with ETE were
genotyped as follows: BRAFV600E, 39 (70%); BRAFV600E-AKT1, 1 (1.8%); NRAS, 1 (1.8%); KRAS, 1 (1.8%);
RET/PTC, 3 (5%); wild type, 11 (19.6%). Within PTCs, BRAF positivity rate increased the risk of ETE (p = 0.01).
If PTC follicular variants are excluded, BRAF positivity does not correlate with ETE status within classical/tall cell
PTC. CONCLUSION: (i) PTCs with METE without NMP have an extremely low recurrence rate in contrast to
tumors with gross ETE. (ii) High mitotic activity and/or tumor necrosis confers worse DSS even in patients
stratified for gross ETE in trachea/esophagus. (iii) BRAF positivity correlates with the presence of ETE in PTC,
but this relationship is lost within classical/tall cell PTC if follicular variants are excluded from the analysis.
PubMed-ID: 20860430

Loss of Raf-1 Kinase Inhibitor Protein Expression Is Associated With Lymph Node Metastasis in
Papillary Thyroid Cancer.
 Otolaryngol Head Neck Surg, 143(4):544-8.
Eun YG, Kim SW, Kim YW, Kwon KH. 2010.
OBJECTIVE: Raf-1 kinase inhibitor protein has potential as a molecular determinant of tumor metastasis and
may serve as a prognostic marker. The aim of this study is to analyze the correlation between Raf-1 kinase
inhibitor protein expression and the clinicopathologic characteristics of papillary thyroid cancer. STUDY DESIGN:
Immunohistochemical analysis. SETTING: Tertiary care teaching hospital. SUBJECTS AND METHODS: Fifty-
nine patients with papillary thyroid cancer underwent total thyroidectomy and central neck dissection. Using
specimens from total thyroidectomy and central neck dissection, we performed immunohistochemistry for Raf-1
kinase inhibitor protein and evaluated associations between Raf-1 kinase inhibitor protein expression and lymph
node metastasis, tumor size, number of tumors, extrathyroidal invasion, angiolymphatic invasion, and status of
the tumor border. RESULTS: We found significantly low Raf-1 kinase inhibitor protein expression in papillary
thyroid cancer with lymph node metastasis. However, Raf-1 kinase inhibitor protein expression was not
associated with tumor size, multifocality, extrathyroidal invasion, or status of the tumor border. CONCLUSION:
The loss of Raf-1 kinase inhibitor protein expression is associated with lymph node metastasis of papillary
thyroid cancer but not with the progression of primary tumors.
PubMed-ID: 20869566

Shear Wave Elastography: a New Ultrasound Imaging Mode for the Differential Diagnosis of Benign and
Malignant Thyroid Nodules.
J Clin Endocrinol Metab, 95(12):5281-8.
Sebag F, Vaillant-Lombard J, Berbis J, Griset V, Henry JF, Petit P, Oliver C. 2010.
CONTEXT: Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new
technique that estimates tissue stiffness in real time and is quantitative and user independent. OBJECTIVES:
The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with
US. DESIGN: Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE
was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first
analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity,
and microcalcifications (Score 1=US Score), and with the same parameters plus EI (Score 2=US+SWE Score).
For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were
used. RESULTS: A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were
malignant. Mean (+/-sd) EI was 150+/-95 kPa (range, 30-356) in malignant nodules vs. 36+/-30 (range, 0-200)
kPa in benign nodules (P<0.001, Student's t test). For a positive predictive value of at least 80%, characteristics
of tissue elasticity (cutoff, 65 kPa) were: sensitivity=85.2%, and specificity=93.9%. Characteristics of the US
Score were: sensitivity=51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity=97% (95% CI, 93.6; 1).
Characteristics of the US+SWE Score were: sensitivity=81.5% (95% CI, 66.9; 96.1), and specificity=97.0% (95%
CI, 93.6; 1). CONCLUSION: Promising results have been obtained with SWE. This technique may be applied to
multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective
places of SWE, US, and FNA.
PubMed-ID: 20881263

Diagnostic Value of a Cytomorphological Subclassification of Follicular Patterned Thyroid Lesions: a
Study of 927 Consecutive Cases With Histological Correlation.

ESES Review of Recently Published Literature 2010-3                                                   Page 26 of 68
Thyroid, 20(10):1077-83.
Deandrea M, Ragazzoni F, Motta M, Torchio B, Mormile A, Garino F, Magliona G, Gamarra E, Ramunni MJ,
Garberoglio R, Limone PP. 2010.
BACKGROUND: Fine-needle aspiration cytology (FNAC) has proved to be an effective diagnostic tool in patients
with thyroid nodules. Several reporting schemes have been suggested to define the risk of malignancy and
consequent clinical management. To date, however, among lesions showing a follicular pattern, FNAC is still
unable to differentiate between benign and malignant ones. The aim of our study was to evaluate whether a
subclassification of follicular cytologic specimens, based on cytoarchitectural patterns, could differentiate
categories with a different risk of malignancy, thus improving the clinical management of patients harboring
follicular nodules. METHODS: We report a cohort of 927 consecutive cases who underwent thyroid surgery in
our hospital between 2000 and 2008. Each patient underwent FNAC before surgery. All the cytologic specimens
were divided into five categories (Thy 1: inadequate material, Thy 2: benign, Thy 3: indeterminate, Thy 4:
suspicious for malignancy, Thy 5: malignant). Thy3 specimens were further divided into three subcategories (Thy
3a, or "follicular lesions of indeterminate significance": scant colloid, microfollicular pattern, or small clusters of
thyrocytes with round nuclei usually without, but sometimes with, minimal cellular pleomorphism; Thy 3b, or
"follicular neoplasm": absence of colloid, small clusters, or microfollicles of medium-large sized cell populations
arranged in cohesive groups with nuclear overlapping, crowding, and pleomorphisms; and Thy 3c or "Hurthle-
cell neoplasm": scant colloid, sheets or clusters of oxyphilic cells). RESULTS: Thy 1 specimens (51 cases on the
whole) proved to be malignant in 5.88% (3 cases), Thy 2 specimens (319) in 3.45% (11 cases), Thy 4
specimens (91) in 84.62% (77 cases), and Thy 5 specimens (172) in 98.84% (170 cases). Thy 3 specimens (294
cases) proved to be malignant in 17.35% as a whole, but when divided into the three subcategories, the
percentage of malignant cases was significantly different between the Thy 3a group (4.95%) and the Thy 3b and
Thy 3c groups (25.0% and 22.77% respectively). CONCLUSIONS: This study supports the National Cancer
Institute consensus showing a different risk of malignancy for "follicular lesions of undetermined significance"
compared with "follicular neoplasms" and "Hurthle cells neoplasms," which are more suspect for malignancy.
This subclassification could improve clinical management of thyroid nodules, helping to better select patients for
surgery or follow up.
PubMed-ID: 20883171

Global Variation in the Pattern of Differentiated Thyroid Cancer.
Am J Surg, 200(4):462-6.
Woodruff SL, Arowolo OA, Akute OO, Afolabi AO, Nwariaku F. 2010.
BACKGROUND: The prevalence of differentiated thyroid cancer (DTC) is increasing worldwide. Iodine
deficiency is a risk factor for follicular thyroid cancer (FTC). We compared DTC subtypes in an iodine-deficient
country with a developed country. METHODS: A retrospective review of thyroid cancer at tertiary centers in West
Africa and the United States. All patients diagnosed with thyroid cancer from 1980 to 2004 were retrieved from
the West African Center's Cancer Registry Database. The study period was divided into two groups: 1980 to
1989 and 1990 to 2004. In the American center, a review of patients undergoing surgery for thyroid cancer from
1997 to 2008 was performed. RESULTS: At the African institution, 322 patients underwent thyroidectomy for
cancer from 1980 to 2004. Overall, 31.5% had papillary thyroid cancer (PTC), and 30.3% had FTC. From 1980
to 1989, 27.3% had PTC and 35.8% had FTC. From 1990 to 2004, 35.7% had PTC and 24.8% had FTC. At the
American institution, 105 patients underwent surgery for thyroid cancer from 1997 to 2008; 79% had PTC and
7.6% had FTC. CONCLUSIONS: FTC is still common in developing countries, whereas PTC is the predominant
subtype in developed countries. Efforts to decrease iodine deficiency may improve outcomes by changing to a
less aggressive subtype.
PubMed-ID: 20887838

Surgical Treatment of Thyroid Diseases in Elderly Patients.
Am J Surg, 200(4):467-72.
Raffaelli M, Bellantone R, Princi P, De CC, Rossi ED, Fadda G, Lombardi CP. 2010.
BACKGROUND: We evaluated the safety of thyroid surgery in elderly patients, in whom surgical procedures
usually are considered more hazardous than in younger patients. METHODS: The medical records of all the
patients who were aged 70 years or older who had undergone thyroid surgery between January 1998 and June
2008 were reviewed. RESULTS: A total of 320 patients were included. The preoperative diagnosis was
multinodular goiter in 171 cases, toxic goiter in 59 cases, suspicious or indeterminate thyroid nodule in 60 cases,
and thyroid carcinoma in 30 patients. Total thyroidectomy was performed in 283 patients, thyroid lobectomy in 15
patients, and a completion thyroidectomy was performed in 22 patients. The final histology showed thyroid

ESES Review of Recently Published Literature 2010-3                                                    Page 27 of 68
cancer in 86 patients and benign disease in 234. CONCLUSIONS: Thyroid surgery in patients aged 70 years or
older is safe and the relatively high rate of thyroid carcinoma and toxic goiter may justify an aggressive
PubMed-ID: 20887839

Search for Genetic Mutations in Cytological Samples From Thyroid Nodules As a Diagnostic Tool:
Reality, Hope or Myth?
J Endocrinol Invest, 33(8):576-8.
Pacini F, Cantara S, Capezzone M. 2010.
PubMed-ID: 20930496

Robot Assisted Transaxillary Surgery (RATS) for the Removal of Thyroid and Parathyroid Glands.
Landry CS, Grubbs EG, Stephen MG, Turner NS, Christopher HF, Lee JE, Perrier ND. 2010.
BACKGROUND: Robotic assisted transaxillary surgery (RATS) is a minimally invasive approach for the removal
of the thyroid and/or parathyroid glands through the axilla. This anatomically directed technique, popularized by
Chung, eliminates a visible scar and affords excellent high definition optics of the cervical anatomy. We report an
initial series of single access RATS in the U.S. METHODS: The prospective endocrine surgery database at a
tertiary care center was used to capture all patients who underwent RATS between October 2009 and March
2010. All procedures were performed using a single transaxillary incision. RESULTS: Fourteen operations were
performed on 13 patients. Indications for RATS were indeterminate thyroid nodules in 11 patients, the need for
completion thyroidectomy in 1 patient, and primary hyperparathyroidism in 2 patients. For patients who
underwent robotic assisted thyroid lobectomy, the median thyroid nodule size was 2.1 cm (range, 0.8-2.8 cm),
and the median body mass index was 25.33 (range, 21.3-34.4). Mean and median total operative times for
robotic assisted thyroid lobectomies were 142 minutes and 137 minutes respectively (range, 113-192 minutes).
Operative time for the 2 patients who underwent robotic assisted parathyroidectomy was 115 and 102 minutes.
Minor complications occurred in 4 patients (28.5%), with no significant perioperative morbidity or mortality.
CONCLUSION: RATS is feasible. We believe that further study of the RATS technique for removing thyroid
lobes and parathyroid glands is warranted. This initial series suggests that careful, continued investigation is
necessary prior to routine implementation into clinical practice across the U.S.
PubMed-ID: 20947113

Postoperative Hypocalcemia After Thyroidectomy for Graves' Disease.
Thyroid, 20(11):1279-83.
Pesce CE, Shiue Z, Tsai HL, Umbricht CB, Tufano RP, Dackiw AP, Kowalski J, Zeiger MA. 2010.
BACKGROUND: It is believed that patients who undergo thyroidectomy for Graves' disease are more likely to
experience postoperative hypocalcemia than patients undergoing total thyroidectomy for other indications.
However, no study has directly compared these two groups of patients. The aim of this study was to determine
whether there was an increased incidence or severity of postoperative hypocalcemia in patients who underwent
thyroidectomy for Graves' disease. METHODS: An institutional review board-approved database was created of
all patients who underwent thyroidectomy from 1998 to 2009 at the Johns Hopkins Hospital. There were a total
of 68 patients with Graves' disease who underwent surgery. Fifty-five patients who underwent total
thyroidectomy were randomly selected and served as control subjects. An analysis was conducted that
examined potential covariates for postoperative hypocalcemia, including age, gender, ethnicity, preoperative
alkaline phosphatase level, size of goiter, whether parathyroid tissue or glands were present in the specimen,
and the reason the patient underwent surgery. Specific outcomes examined were calcium levels on
postoperative day 1, whether or not patients experienced symptoms of hypocalcemia, whether or not Rocaltrol
was required, the number of calcium tablets prescribed upon discharge, whether or not postoperative tetany
occurred, and calcium levels 1 month after discharge. RESULTS: Each outcome was analyzed using a logistic
regression. Graves' disease patients had a significantly (p-value < 0.001) higher odds of greater number of
calcium tablets prescribed upon discharge. Further, 6 of 68 patients with Graves' disease and no patient in the
control group were readmitted with tetany (p = 0.033). There was a trend, though not significant, toward patients
with Graves' disease having a higher prevalence of hypocalcemia the day after thyroidectomy and 1 month later.
CONCLUSIONS: Patients with Graves' disease are more likely to require increased dosages of calcium as well
as experience tetany postoperatively than patients undergoing total thyroidectomy for other indications. This
suggests that patients operated upon for Graves' disease warrant close followup as both inpatients and
outpatients for signs and symptoms of hypocalcemia.

ESES Review of Recently Published Literature 2010-3                                                 Page 28 of 68
PubMed-ID: 20950255

The BRAF Mutation Is Predictive of Aggressive Clinicopathological Characteristics in Papillary Thyroid
Ann Surg Oncol, 17(12):3294-300.
Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. 2010.
BACKGROUND: This study analyzed the utility of BRAF mutation screening of ultrasonography-guided fine-
needle aspiration biopsy (FNAB) specimens for predicting aggressive clinicopathological characteristics of
papillary thyroid microcarcinoma (PTMC). METHODS: We assessed the T1799A BRAF mutation status in FNAB
specimens obtained from 61 PTMC patients before undergoing operations for PTMC. We examined whether the
BRAF mutation was associated with clinicopathologic characteristics in PTMC. Additionally, we reviewed the
BRAF mutation status, and clinical, ultrasound (US), hematological, and pathology records of the patients and
analyzed the associations between these characteristics and lateral lymph node metastasis (LNM). RESULTS:
Analysis of the preoperative FNABs accurately reflected the BRAF status of the resected tissues in 19 of the 20
paired samples (95% concordance). We observed that the BRAF mutation was statistically significantly
associated with multifocality, extrathyroidal invasion, lateral LNM, and advanced tumor stages III and IV. The
BRAF mutation, pathologic features (central LNM), and US features (upper pole location) were independent
predictive factors for lateral LNM in a multivariate analysis with odds ratios of 18.144 (95% confidence interval
[95% CI], 1.999-164.664; P = 0.01), 8.582 (95% CI, 1.014-76.662; P = 0.049) and 9.576 (95% CI, 1.374-66.728;
P = 0.023), respectively. CONCLUSIONS: BRAF mutation-positive PTMCs were more likely to manifest
aggressive characteristics (extrathyroidal extension and LNM). The BRAF mutation screening of FNAB
specimens can be used to predict aggressive clinicopathological characteristics of PTMC. Lateral neck nodes
should be meticulously analyzed for cases of PTMC demonstrating the following three characteristics: BRAF
mutation, central LNM, and US features in the upper pole location.
PubMed-ID: 20953721

Clinical Characteristics and Outcome of Familial Nonmedullary Thyroid Cancer: a Retrospective
Controlled Study.
Thyroid, 21(1):43-8.
Robenshtok E, Tzvetov G, Grozinsky-Glasberg S, Shraga-Slutzky I, Weinstein R, Lazar L, Serov S, Singer J,
Hirsch D, Shimon I, Benbassat C. 2011.
BACKGROUND: Familial nonmedullary thyroid cancer (FNMTC) is a disease defined by clustering of thyroid
cancers of follicular cell origin, and it is estimated to account for 5% of all thyroid cancers. Several studies found
FNMTC to be more aggressive than sporadic disease, whereas others found them to have a similar course and
outcome. The purpose of this study was to determine whether FNMTC is more aggressive than sporadic thyroid
cancer. METHODS: A retrospective controlled study of FNMTC versus sporadic nonmedullary thyroid cancers
was conducted using a registry of patients with thyroid cancer. Data on disease severity at presentation,
treatment modalities, and outcome were collected. RESULTS: Sixty-seven patients with FNMTC and 375
controls with sporadic disease were included. Follow-up period was 8.6 +/- 10 years for patients with FNMTC
and 8.4 +/- 9.1 years for sporadic cases. Patients with FNMTC had comparable disease severity at diagnosis as
sporadic patients, underwent similar surgical and radioiodine treatments, and had similar long-term disease-free
survival. Long-term outcome in families with three or more affected relatives was similar to families with only two
affected relatives. CONCLUSIONS: Our results suggest that FNMTC is not more aggressive than sporadic
thyroid cancer within our studied population. After a similar therapeutic strategy, FNMTC and sporadic cases had
comparable prognosis, including in families with three or more affected members.
PubMed-ID: 20954815

Sorafenib: Rays of Hope in Thyroid Cancer.
Thyroid, 20(12):1351-8.
Duntas LH, Bernardini R. 2010.
BACKGROUND: Sorafenib (BAY 43-9006) is an inhibitor of multiple-receptor tyrosine kinases involved in tumor
growth and angiogenesis, which can be advantageously administered orally. Initially used as monotherapy in
advanced renal cell carcinoma, sorafenib was proven to increase progression-free survival while enhancing
disease control. Clinical trials on sorafenib are at present ongoing for the treatment of various malignancies,
including thyroid cancer (TC). SUMMARY: Specifically, in two phase II studies recently conducted on papillary
TC, although the respective results were not entirely compatible as regard partial response rate and progression-

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free survival, sorafenib demonstrated a relatively favorable benefit/risk profile. In another more recent phase II
study, whose primary endpoint was the reinduction of radioactive iodine uptake at 26 weeks, although no
reinduction of radioactive iodine uptake was observed, 59% had a beneficial response and 34% had stable
disease. Sorafenib hence appears to be a valid alternative to conventional treatment of metastatic papillary TC
refractory to radioiodine therapy. CONCLUSIONS: Further prospective investigations are required to define the
characteristics of tumor response to the drug and the factors inducing resistance to treatment. A major issue
demanding immediate attention involves optimization of sorafenib treatment: this concerns multidrug
combination with different tyrosine kinase inhibitors or immunomodulating agents with the aim of reducing doses
and thereby improving drug tolerability and antineoplastic capability.
PubMed-ID: 20954817

Intra- and Postoperative Parathyroid Hormone-Kinetics Do Not Advocate for Autotransplantation of
Discolored Parathyroid Glands During Thyroidectomy.
Thyroid, 20(12):1371-5.
Promberger R, Ott J, Kober F, Mikola B, Karik M, Freissmuth M, Hermann M. 2010.
BACKGROUND: Thyroidectomy continues to pose the risk of typical complications, including postoperative
hypocalcemia and permanent hypoparathyroidism. The strategic decision on how to preserve parathyroid
hormone (PTH) secretion relies on assessing the viability of the parathyroid glands (PGs). The aim of this study
was to assess parathyroid discoloration as an indicator for loss of parathyroid function. METHODS: The
prospective study included 29 patients (24 women, 5 men; age 53.2 +/- 13.0 years) who underwent near-total or
total thyroidectomy. An intra- and postoperative PTH and calcium monitoring was performed. The intraoperative
situs of the PGs was documented by a study protocol. The patients were grouped in three categories: group A,
12 patients with four visualized and normally colored PGs; group B, 13 patients with four visualized and three or
four discolored PGs; group C, 4 patients who had undergone autotransplantation of two PGs. RESULTS:
Compared to group A, groups B and C showed sharper intraoperative PTH declines. PTH values recovered
more quickly in group B than in group C. However, no significant differences in PTH kinetics were found in the
general linear model for repeated measures (p = 0.132). However, a significantly higher incidence of protracted
hypocalcemia-related symptoms for more than 14 postoperative days was found for group C (50.0%) than for
groups A (0%) and B (0%; p = 0.011). None of the patients developed permanent hypoparathyroidism.
CONCLUSIONS: The function of discolored PGs is only transiently impaired and recovers within a short time
after surgery. Our observations do not support autotransplantation as a generally applicable first-line intervention
for discolored PGs in the absence of other criteria for autotransplantation.
PubMed-ID: 20954822

Radioguided Surgery Using an Intraoperative PET Probe for Tumor Localization and Verification of
Complete Resection in Differentiated Thyroid Cancer: A Pilot Study.
Surgery, 149(3):416-24.
Kim WW, Kim JS, Hur SM, Kim SH, Lee SK, Choi JH, Kim S, Choi JY, Lee JE, Kim JH, Nam SJ, Yang JH, Choe
JH. 2011.
BACKGROUND: The major concerns in the surgical treatment of extensive or recurrent thyroid cancer include
the difficulty of precise intraoperative and real-time tumor localization, the possibility of missing small metastatic
lymph nodes during the operation, the need for reoperation due to recurrence, and complications. The
usefulness and feasibility of an intraoperative PET probe have been reported for many other cancers; however,
a standard, radioguided, operative protocol using a PET probe in thyroid cancer has not been established. The
purpose of the current study was to evaluate the feasibility of an intraoperative PET probe with respect to
precise tumor localization, verification of complete resection, and a decrease in unnecessary reoperations and
complications. METHODS: This was a prospective, controlled study. Inclusion criteria were thyroid cancer
requiring a total thyroidectomy with a modified radical neck dissection (MRND) and recurrent thyroid cancer after
thyroid surgery. The types of procedures included total thyroidectomy with MRND, selective neck dissection
(SND), and excision of recurrent thyroid masses. The PET probe NodeSeeker((R)) is a high-energy gamma
probe seeking 511 keV photons. Operative exploration was carried out between 2 and 6 h after injection of
(18)F-FDG. The surgeon calculated the target-to-background ratio (T/B ratio) by checking the 10-sec
accumulated count using the PET probe. We performed a re-exploration if the T/B ratio was >1.3 in the operative
bed. RESULTS: Twelve patients underwent PET probe-guided operation. SNDs, mass excisions, total
thyroidectomy with MRND, and MRND were performed on 7, 4, and 1 patient, respectively. All tumors were
localized by the PET probe precisely in real time, and the lesions not observed on preoperative PET were
detected by the PET probe in 7 patients. Furthermore, additional lymph nodes that were not identified on

ESES Review of Recently Published Literature 2010-3                                                   Page 30 of 68
preoperative ultrasonography were detected in 1 patient. The mean T/B ratio of thyroid carcinoma was 1.51 +/-
0.53 (range, 1.17-4.03) and the postoperative serum thyroglobulin off thyroid hormone was <2.0 ng/ml.
CONCLUSION: Radioguided surgery using an intraoperative PET probe in thyroid cancer appears to be a useful
method for real-time tumor localization, verification of complete excision, and minimization of the possibility of
residual cancer. Therefore, an intraoperative PET probe in thyroid cancer may decrease unnecessary
reoperations and complications due to persistent disease.
PubMed-ID: 20965536

Discordance Between Cytologic Results in Multiple Thyroid Nodules Within the Same Patient.
Acta Cytol, 54(5):673-8.
Levenson JN, Santaella I, Wachtel MS, Levenson DI. 2010.
OBJECTIVE: To examine the frequency of discordant cytologic results between multiple thyroid nodules
biopsied in the same patient. STUDY DESIGN: In a retrospective chart review of 441 consecutive patients, 326
(73.9%) had 2 or more nodules with colloid and/or thyroid cells recovered. Cytology was classified as (A) colloid
only, (B) benign colloid nodule with or without degeneration, (C) Hashimoto's, or (D) follicular or Hurthle cell
neoplasm, hyperplasia or suspicious for malignancy. Discordance was defined as having at least 2 different
categories in the same patient. Twenty-four predetermined factors were analyzed, including demographics,
laboratory values and ultrasound characteristics. RESULTS: The results, by category, were A, 164 (18.4%); B,
575 (64.6%); C, 131 (14.7%); and D, 20 (2.2%). Overall, 126 of 326 (38.7%) patients had at least 1 discordant
grouping between their nodules. Of 326 patients, 165 had 2, 94 had 3, 48 had 4, 14 had 5, and 5 had 6 nodules
biopsied, of which 48 (29.1%), 39 (41.5%), 29 (60.4%), 8 (57.1%) and 2 (40.0%), respectively, showed
diagnostic discordances (p = 0.0007). CONCLUSION: The high rate (38.7%) of discordance between biopsies of
multiple nodules in the same patient support a recommendation to biopsy all nodules that otherwise meet criteria
for biopsy, as opposed to only the largest one.
PubMed-ID: 20968154

Endoscopic Completion Thyroidectomy by the Bilateral Axillo-Breast Approach.
Surg Laparosc Endosc Percutan Tech, 20(5):312-6.
Kim SJ, Lee KE, Choe JH, Lee J, Koo dH, Oh SK, Youn YK. 2010.
PURPOSE: Bilateral axillo-breast approach (BABA) endoscopic thyroidectomy has been successfully used for
various thyroid diseases, with an excellent cosmetic outcome. Patients with a confirmed thyroid malignancy on a
permanent thyroid section after endoscopic thyroid lobectomy require completion thyroidectomy. Here, we
sought to demonstrate the feasibility of endoscopic completion thyroidectomy by BABA. PATIENTS AND
METHODS: Between June, 2006 and February, 2009, 13 patients underwent endoscopic completion
thyroidectomy by BABA for minimally invasive follicular thyroid and papillary thyroid carcinomas diagnosed after
BABA endoscopic thyroid lobectomy. The median interval between thyroid lobectomy and completion
thyroidectomy was 5.6 months (range, 4.2-28.2 mo). We used the same port sites (bilateral breast and axillary
region) as were created at the initial operation. Flap adhesion was minimal. After identifying the remnant thyroid
lobe, completion thyroidectomy was performed under full visualization of the thyroidal vessels, parathyroid
glands, and recurrent laryngeal nerve. RESULTS: We performed 5 right and 8 left endoscopic completion
thyroidectomies by BABA. The mean operation time was 109.3+/-23.3 minutes. There were no cases of open
conversion. The resulting 6 (46.2%) cases of transient hypocalcemia resolved within 2 postoperative weeks and
there were no cases of vocal cord palsy or wound infection. One patient had immediate postoperative breast flap
bleeding that required cauterization. No patient had evidence of recurrence, as indicated by follow-up neck
ultrasonography and serum thyroglobulin levels. The cosmetic outcomes were excellent and all patients were
satisfied. CONCLUSIONS: BABA endoscopic thyroidectomy appears feasible and safe procedure for completion
thyroidectomy, making it a viable technique for reapplication in cases of thyroid carcinoma diagnosed after
endoscopic thyroid lobectomy.
PubMed-ID: 20975501

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and
Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk
Estimates Predicted by the New American Thyroid Association Staging System.
Thyroid, 20(12):1341-9.
Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A. 2010.
BACKGROUND: A risk-adapted approach to management of thyroid cancer requires risk estimates that change
over time based on response to therapy and the course of the disease. The objective of this study was to

ESES Review of Recently Published Literature 2010-3                                                Page 31 of 68
validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an
assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates.
METHODS: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed
for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation.
Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging.
Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and
imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable,
or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk
estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates.
RESULTS: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the
intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-
up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in
intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg
< 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy
(suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within
the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in
low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS: Our data confirm that the
newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent
disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of
response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively
tailor ongoing follow-up recommendations.
PubMed-ID: 21034228

Medullary Thyroid Carcinoma, Small Cell Variant, As a Diagnostic Challenge on Fine Needle Aspiration:
a Case Report.
Acta Cytol, 54(5 Suppl):911-7.
Yerly S, Triponez F, Meyer P, Kumar N, Bongiovanni M. 2010.
BACKGROUND: The small cell variant of medullary thyroid carcinoma (SCV-MTC) is a very unusual tumor that
carries a poor prognosis. This tumor type closely resembles small cell pulmonary neuroendocrine carcinoma or
lymphoma. CASE: A 43-year-old woman had a palpable mass on the right side of her neck. A fine needle
aspiration biopsy (FNAB) revealed a hypercellular lesion composed mainly of isolated, small, round cells with
salt-and-pepper chromatin interspersed with inconspicuous deposits of fluffy acellular material. A diagnosis of
"malignant tumor, consistent with small cell carcinoma, metastasis not excluded" was rendered during the on-
site rapid cytologic examination. Immunostaining showed a few isolated cells reactive for calcitonin, intense and
diffuse immunoreactivity for carcinoembryonic antigen, dotlike positivity for chromogranin and cytokeratin, and
negativity for thyroglobulin. Congo-red staining was positive in the acellular deposit, consistent with SCV-MTC.
Subsequent total thyroidectomy confirmed this diagnosis. CONCLUSION: The wide range of cytomorphologic
features of MTC can be misleading on FNAB and can be a diagnostic challenge. Congo-red staining and
immunoreactivity for calcitonin can be negative in this variant. Consequently, salt-and-pepper chromatin, Congo-
red staining and a panel of antibodies comprising calcitonin, carcinoembryonic antigen, chromogranin,
cytokeratin, leukocyte common antigen and thyroglobulin are mandatory for the correct diagnosis.
PubMed-ID: 21053568

Radioiodine Therapy in Patients With Stage I Differentiated Thyroid Cancer.
Thyroid, 20(12):1423-4.
Jonklaas J, Cooper DS, Ain KB, Bigos T, Brierley JD, Haugen BR, Ladenson PW, Magner J, Ross DS, Skarulis
MC, Steward DL, Maxon HR, Sherman SI. 2010.
PubMed-ID: 21054207

The Effectiveness of Radioactive Iodine for Treatment of Low-Risk Thyroid Cancer: a Systematic
Analysis of the Peer-Reviewed Literature From 1966 to April 2008.
Thyroid, 20(11):1235-45.
Sacks W, Fung CH, Chang JT, Waxman A, Braunstein GD. 2010.
BACKGROUND: Radioactive iodine (RAI) remnant ablation has been used to eliminate normal thyroid tissue
and may also facilitate monitoring for persistent or recurrent thyroid carcinoma. The use of RAI for low-risk
patients who we define as those under age 45 with stage I disease or over age 45 with stage I or II disease
based on American Joint Committee on Cancer (AJCC) 6th edition, or low risk under the metastases, age,

ESES Review of Recently Published Literature 2010-3                                                    Page 32 of 68
completeness of resection, invasion, size (MACIS) staging system (value <6) is controversial. In this extensive
literature review, we sought to analyze the evidence for use of RAI treatment to improve mortality and survival
and to reduce recurrence in patients of various stages and disease risk, particularly for those patients who are at
low risk for recurrence and death from thyroid cancer. METHODS: A MEDLINE search was conducted for
studies published between January 1966 and April 2008 that compared the effectiveness of administering
versus not administering RAI for treatment of differentiated thyroid cancer (DTC). Studies were grouped A
through D based on their methodological rigor (best to worst). An analysis, focused on group A studies, was
performed to determine whether treatment with RAI for DTC results in decreased recurrences and improved
survival rates. RESULTS: The majority of studies did not find a statistically significant improvement in mortality or
disease-specific survival in those low-risk patients treated with RAI, whereas improved survival was confirmed
for high-risk (AJCC stages III and IV) patients. Evidence for RAI decreasing recurrence was mixed with half of
the studies showing a significant relationship and half showing no relationship. CONCLUSIONS: We propose a
management guideline based on a patient's risk-very low, low, moderate, and high-for clinicians to use when
delineating those patients who should undergo RAI treatment for initial postoperative management of DTC. A
majority of very low-risk and low-risk patients, as well as select cases of patients with moderate risk do not
demonstrate survival or disease-free survival benefit from postoperative RAI treatment, and therefore we
recommend against postoperative RAI in these cases.
PubMed-ID: 21062195

Robotic Thyroidectomy: a Framework for New Technology Assessment and Safe Implementation.
Thyroid, 20(12):1327-32.
Perrier ND, Randolph GW, Inabnet WB, Marple BF, VanHeerden J, Kuppersmith RB. 2010.
Robotic thyroidectomy is a new approach to thyroid surgery that offers the benefit of eliminating the anterior neck
incision utilized in traditional approaches. Although no level I evidence exists to strongly support a robotic
approach to thyroid surgery, initial non-randomized reports of robotic surgical approaches, in a variety of surgical
specialty areas such as cardiothoracic, urologic, gynecologic and head and neck surgery suggest possible
advantages of robot assisted techniques. These include platform and instrument stability, tremor reduction,
articulating end effectors, three-dimensional, magnified imaging, and improved surgeon ergonomics. Potential
negatives associated with robotic surgery include its expense, the lack of haptic feedback, instrument limitations,
and the implicit learning curve. Robotic thyroidectomy introduces new potential risks, not typically associated
with thyroid surgery. These risks are related to a new approach to the surrounding anatomy and are also
associated with the learning curve. The introduction of new technology to any surgery mandates a rational
framework for initial assessment and safe implementation. A New Technology Task Force was convened to draft
guiding principles which may serve as a framework for the safe implementation of emerging technologies in
thyroid surgery. This document suggests initial minimum steps that surgeons should consider during initial
implementation of robotic thyroidectomy.
PubMed-ID: 21114381

Approach to Management of the Patient With Primary or Secondary Intrathoracic Goiter.
J Clin Endocrinol Metab , 95(12):5155-62.
Hegedus L, Bonnema SJ. 2010.
Intrathoracic (substernal) goiter, depending on definition, is seen in up to 45% of all patients operated for goiter.
It can either be primary (ectopic thyroid tissue detached from a cervical thyroid mass), which is very rare (1%), or
(more commonly) secondary, where a portion of the goiter extends retrosternally. There is no consensus on
diagnostic or therapeutic management, partly because many are asymptomatic. Classification involves functional
characterization with serum TSH and morphological characterization with diagnostic imaging and cytology to rule
out malignancy, which is not more common than in cervical goiters. Pulmonary function is often affected in
asymptomatic individuals also. Therefore, but also because natural history is continuous growth and evolution
from euthyroidism to hyperthyroidism, most experts recommend therapy. In primary as well as secondary
intrathoracic goiter, the therapy of choice is total/near-total thyroidectomy and subsequent levothyroxine
substitution. Data suggest that complications are only slightly more prevalent than in cervical goiters. Although
levothyroxine is not recommended for goiter shrinkage, there is increasing focus on radioactive iodine as an
alternative to surgery in secondary intrathoracic goiters. Here it can reduce thyroid size by on average 40% after
1 yr and improve respiratory function and quality of life. Recent studies show that recombinant human TSH,
currently used off-label, can augment the radioiodine-related goiter shrinkage by 30-50%. With currently used
doses of recombinant human TSH, the side effects, besides hypothyroidism, are rare and mild. Future studies
should also explore the use of radioiodine in primary intrathoracic goiter and compare surgery and radioiodine,

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head to head.
PubMed-ID: 21131536

Analysis of the Rising Incidence of Thyroid Cancer Using the Surveillance, Epidemiology and End
Results National Cancer Data Registry.
Surgery, 148(6):1147-52.
Cramer JD, Fu P, Harth KC, Margevicius S, Wilhelm SM. 2010.
BACKGROUND: The incidence of thyroid cancer has more than doubled in recent decades. Debate continues
on whether the increasing incidence is a result of an increased detection of small neoplasms or other factors.
METHODS: Using the Surveillance, Epidemiology and End Results database, we examined the overall
incidence of thyroid cancer with variations based on tumor pathology, size, and stage, as well as the current
surgical and adjuvant therapy of thyroid carcinoma. RESULTS: Thyroid cancer incidence increased 2.6-fold from
1973 to 2006. This change can be attributed primarily to an increase in papillary thyroid carcinoma, which
increased 3.2-fold (P < .0001). The increase in papillary thyroid carcinoma also was examined based on tumor
size. Tumors </= 1 cm increased the most at a total of 441% between 1983 and 2006 or by 19.2% per year, the
incidence of papillary thyroid carcinoma also increased at 12.3%/year in 1.1-2-cm tumors, 10.3%/year in 2.1-5-
cm tumors, and 12.0%/year for > 5-cm tumors (all P < .0001 by Cochran-Armitage trend test). We also
demonstrated a positive correlation between papillary thyroid carcinoma tumor size and stage of disease
(Spearman, r = 0.285, P < .0001). Operative treatment for thyroid cancer also has shifted with total
thyroidectomy replacing partial thyroidectomy as the most common surgical procedure. CONCLUSION: Contrary
to other studies, our data indicate that the increasing incidence of thyroid cancer cannot be accounted for fully by
an increased detection of small neoplasms. Other possible explanations for the increase in clinically significant
(> 1 cm) well-differentiated thyroid carcinomas should be explored.
PubMed-ID: 21134545

Is DVT Prophylaxis Necessary for Thyroidectomy and Parathyroidectomy?
Surgery, 148(6):1163-8.
Roy M, Rajamanickam V, Chen H, Sippel R. 2010.
BACKGROUND: Recent guidelines suggest pharmacologic deep vein thrombosis (DVT) prophylaxis in all
patients undergoing major surgical procedures to minimize the risk of postoperative DVT and pulmonary
embolism (PE). Pharmacologic DVT prophylaxis perioperatively might increase the risk of bleeding
complications. Our goal was to study the risk/benefit ratio of DVT prophylaxis in patients who undergo
thyroidectomy and parathyroidectomy. METHODS: A review of the ACS NSQIP Database from 2005 to 2007
was performed. The incidence of DVT/PE complications in a cohort of 347,862 patients was compared with the
16,022 patients who underwent a thyroidectomy or parathyroidectomy. We identified risk factors for DVT/PE and
developed a surrogate variable to determine the risk for postoperative bleeding. RESULTS: The risk of DVT/PE
complication in the thyroidectomy and parathyroidectomy patients (0.16) was 6 fold less than the entire cohort
(0.96) (P < .001). The estimated risk of bleeding requiring a return to the operating room was 1.58%, which is
10-fold greater than the risk of developing a DVT/PE (P < .001). CONCLUSION: Patients who underwent
thyroidectomy and parathyroidectomy have a low incidence of developing DVT/PE complications and have a
significantly greater risk of developing bleeding complications. Hence, we believe that DVT prophylaxis should
be done at the discretion of the surgeon in select high-risk patients only.
PubMed-ID: 21134547

A Prospective Study Evaluating the Accuracy of Using Combined Clinical Factors and Candidate
Diagnostic Markers to Refine the Accuracy of Thyroid Fine Needle Aspiration Biopsy.
Surgery, 148(6):1170-6.
Mathur A, Weng J, Moses W, Steinberg SM, Rahabari R, Kitano M, Khanafshar E, Ljung BM, Duh QY, Clark
OH, Kebebew E. 2010.
BACKGROUND: Approximately 30% of fine needle aspiration biopsies of the thyroid have inconclusive results.
We conducted a prospective trial to determine whether clinical and molecular markers could be used in
combination to improve the accuracy of thyroid fine needle aspiration biopsy. METHODS: Clinical, tumor
genotyping for common somatic mutations (BRAF V600E, NRAS, KRAS, RET/PTC1, RET/PTC3, and NTRK1),
and the gene expression levels of 6 candidate diagnostic markers were analyzed by univariate and multivariate
methods in 341 patients to determine whether they could distinguish reliably benign from malignant thyroid
neoplasms, and a scoring model was derived. RESULTS: By a multivariate analysis, fine needle aspiration

ESES Review of Recently Published Literature 2010-3                                                 Page 34 of 68
biopsy cytology classification, the presence of a NRAS mutation, and the tissue inhibitor of metalloproteinase 1
expression level were associated jointly with malignancy. The overall accuracy of the scoring model, including
these 3 variables, to distinguish benign from malignant thyroid tumors was 91%, including 67% for the
indeterminate and 77% for the suspicious FNA subgroups. CONCLUSION: Fine needle aspiration biopsy
cytology classification, the presence of NRAS mutation, and tissue inhibitor of metalloproteinase 1 messenger
RNA expression levels in combination provide a greater diagnostic accuracy than fine needle aspiration biopsy
cytology alone to allow selection of more definitive initial operative treatment. The sensitivity of the scoring
model, however, was too low to avoid the need for diagnostic thyroidectomies for indeterminate fine needle
aspiration biopsy findings.
PubMed-ID: 21134548

Impact of Second Primary Malignancy on Outcomes of Differentiated Thyroid Carcinoma.
Surgery, 148(6):1191-6.
Lang BH, Lo CY, Wong IO, Cowling BJ. 2010.
BACKGROUND: There are few data on the degree to which thyroid cancer survivors are at risk of second
primary malignancy (SPM). This study aimed at evaluating the risk of SPM in patients with differentiated thyroid
carcinoma (DTC) and how the timing of SPM might affect the disease course. METHODS: Among 1,043 patients
diagnosed with DTC between 1970 and 2008, 27 (2.6%) had synchronous SPM (ie, diagnosed within 6 months
of DTC) and 71 (6.8%) had metachronous SPM (ie, diagnosed > 6 months after DTC) in 10,419 person-years of
follow-up. Standardized incidence ratios were estimated overall and for each SPM site. RESULTS: DTC
survivors had a 39% greater risk of SPM (SIR = 1.39; 95% CI, 1.09-1.73) compared to the general population.
Those with SPM had a worse overall survival than those without SPM (P < .001). The synchronous group had a
worse DTC-specific survival (P = .002), whereas the metachronous group had a worse SPM-specific survival (P
= .042). A lesser proportion in the metachronous group were able to receive curative treatment for SPM (32/71
vs 20/27; P = .013). CONCLUSION: DTC survivors had an increased risk of SPM. The occurrence of SPM
adversely affected the survival of DTC. The synchronous group tended to die from DTC, whereas the
metachronous group from SPM. Heightened postoperative surveillance might improve survival.
PubMed-ID: 21134551

Management of Cervical Nodal Metastasis Detected on I-131 Scintigraphy After Initial Surgery of Well-
Differentiated Thyroid Carcinoma.
Surgery, 148(6):1198-204.
Creach KM, Gillanders WE, Siegel BA, Haughey BH, Moley JF, Grigsby PW. 2010.
BACKGROUND: The purpose of this study was to evaluate the outcome of patients with differentiated thyroid
carcinoma whose posttherapy imaging demonstrated I-131 uptake in cervical lymph nodes. METHODS: In this
prospective cohort study, 95 patients who underwent surgery for well-differentiated thyroid carcinoma had
evidence of persistent cervical lymph node metastasis on posttherapy I-131 scintigraphy. These patients were
evaluated by subsequent I-131 scintigraphy, and treated with additional I-131 therapy or surgical excision of
cervical lymph nodes as clinically indicated. Patients were followed for a mean of 6.8 years. RESULTS: Patients
received a total of one to three I-131 administrations (median dosage, 235 mCi). Surveillance I-131 scintigraphy
was performed to evaluate disease activity. I-131 uptake was eliminated from the thyroid bed in all patients.
Persistent disease was detected in cervical lymph nodes in 9 (9%) of 95 patients, and these 9 patients
underwent lymph node excision (1 patient later had recurrent disease and was treated with additional I-131
therapy). All patients subsequently had negative I-131 imaging and undetectable serum thyroglobulin. Of the 95
patients in the study, 9 (9%) developed recurrent disease in cervical lymph nodes. Of these 9 patients, 2 also
had distant metastases; 6 of these patients underwent surgical excision of cervical adenopathy, and 3 received
additional I-131 therapy. There were no grade >3 toxicities attributable to I-131. At last follow-up, 93 (98%) of the
95 patients were free of disease. CONCLUSION: Most patients (82%) in the study with cervical lymph node
metastases detected on initial posttherapy I-131 scintigraphy were rendered free of disease with I-131 therapy.
Surgical reintervention was required in 15% of patients (15/95). The use and timing of additional I-131 therapy
versus surgical intervention in this group of patients needs to be further evaluated.
PubMed-ID: 21134552

Outcomes of 109 Patients With Papillary Thyroid Carcinoma Who Underwent Robotic Total
Thyroidectomy With Central Node Dissection Via the Bilateral Axillo-Breast Approach.
Surgery, 148(6):1207-13.

ESES Review of Recently Published Literature 2010-3                                                  Page 35 of 68
Lee KE, Koo dH, Kim SJ, Lee J, Park KS, Oh SK, Youn YK. 2010.
BACKGROUND: We developed the bilateral, axillo-breast approach (BABA) to endoscopic thyroidectomy and
applied it to the da Vinci robotic surgical system in 2008. Herein, we have analyzed the immediate postoperative
outcomes and 1-year follow-up results of robotic BABA total thyroidectomy with central node dissection (CND).
METHODS: In 2008 and 2009, 109 patients with PTC underwent robotic BABA total thyroidectomy with CND.
Clinicopathologic characteristics, short- and long-term complications, and postoperative thyroglobulin (Tg) level
were obtained prospectively and analyzed. RESULTS: The mean age was 39 +/- 10 years and the male to
female ratio was 1:5.8. The mean operation time was 206 +/- 36 minutes. Transient recurrent laryngeal nerve
(RLN) palsy occurred in 17 cases (16%) and transient hypocalcemia in 21 cases (19%). The median follow-up
was 12 months. There were 1 and 2 cases of permanent RLN palsy and permanent hypoparathyroidism,
respectively. Postoperative radioactive iodine ablation was performed on 54 patients (50%). Their mean
stimulated Tg level was 1.84 +/- 6.35 ng/mL and 76% had stimulated Tg levels <1.0 ng/mL. CONCLUSION:
Robotic BABA total thyroidectomy with CND yields good postoperative outcomes. Given the excellent cosmetic
outcomes, this technique may be a suitable operative alternative for low-risk patients with PTC.
PubMed-ID: 21134553

Initial Experience With Robot-Assisted Modified Radical Neck Dissection for the Management of Thyroid
Carcinoma With Lateral Neck Node Metastasis.
Surgery, 148(6):1214-21.
Kang SW, Lee SH, Ryu HR, Lee KY, Jeong JJ, Nam KH, Chung WY, Park CS. 2010.
BACKGROUND: Since the introduction of endoscopic techniques in thyroid surgery, several trials of endoscopic
lateral neck dissection have been conducted with the aim of avoiding a long cervical scar, but these endoscopic
procedures require more effort than open surgery, mainly because of the relatively nonsophisticated instruments
used. However, the recent introduction of surgical robotic systems has simplified the operations and increased
the precision of endoscopic techniques. We have described our initial experience with robot-assisted modified
radical neck dissection (MRND) in thyroid cancer using the da Vinci S system. METHODS: From October 2007
to October 2009, 33 patients with thyroid cancer with lateral neck lymph node (LN) metastases underwent robot-
assisted thyroidectomy and additional robotic MRND using a gasless, transaxillary approach. Clinicopathologic
data were analyzed retrospectively. RESULTS: Mean patient age was 37 +/- 9 years and the gender ratio (male
to female) was 7:26. The mean operating time was 281 +/- 41 minutes and mean postoperative hospital stay
was 5.4 +/- 1.6 days. The mean tumor size was 1.1 +/- 0.5 cm and 20 cases (61%) had papillary thyroid
microcarcinoma. The mean number of retrieved LNs was 6.1 +/- 4.4 in the central neck compartment and 27.7
+/- 11.0 in the lateral compartment. No serious postoperative complications, such as Horner's syndrome or major
nerve injury, occurred. CONCLUSION: Robot-assisted MRND is technically feasible, safe, and produces
excellent cosmetic results. Based on our initial experience, robot-assisted MRND should be viewed as an
acceptable alternative method in patients with low-risk, well-differentiated thyroid cancer with lateral neck node
PubMed-ID: 21134554

Impact of the 2009 American Thyroid Association Guidelines on the Choice of Operation for Well-
Differentiated Thyroid Microcarcinomas.
Surgery, 148(6):1222-6.
Ogilvie JB, Patel KN, Heller KS. 2010.
BACKGROUND: The 2009 ATA Guidelines state "lobectomy alone may be sufficient treatment for small (< 1
cm), low risk, unifocal, intrathyroidal papillary carcinomas in the absence of . . . nodal metastases." We
determined how often these criteria are satisfied, and whether tumor size alone can dictate operative
management. METHODS: Medical records of 346 patients with well-differentiated thyroid cancer (WDTC) who
underwent thyroidectomy from January 1, 2007 to November 10, 2009, were reviewed. There were 130 patients
with tumors </= 1 cm and negative lateral nodes. Pathology reports were reviewed to identify adverse features
including multifocality, extrathyroidal extension, vascular invasion, and central node metastases. RESULTS:
Eighty-four percent underwent total thyroidectomy and 16% central node dissection. All but 2 patients had
papillary cancer. Sixty-one percent with cancers 6-10 mm (group 1) had adverse pathologic features compared
with 32% with cancers < 6 mm (group 2). Multifocality was most common: 55% in group 1 versus 32% in group 2
(P = .004). Positive central nodes were identified in 23% of group 1 versus 4% of group 2 (P = .004). Of patients
in group 1, 88% had positive or suspicious fine-needle aspiration biopsy (FNAB) preoperatively. CONCLUSION:
We recommend that total thyroidectomy be considered as the initial operation for thyroid tumors 6-10 mm in size
in which the preoperative FNAB is diagnostic or suspicious for WDTC.

ESES Review of Recently Published Literature 2010-3                                               Page 36 of 68
PubMed-ID: 21134555

Impact of Extent of Resection for Thyroid Cancer Invading the Aerodigestive Tract on Surgical Morbidity,
Local Recurrence, and Cancer-Specific Survival.
Surgery, 148(6):1257-66.
Brauckhoff M, Machens A, Thanh PN, Lorenz K, Schmeil A, Stratmann M, Sekulla C, Brauckhoff K, Dralle H.
BACKGROUND: The appropriate resection for thyroid cancer invading the aerodigestive tract remains
controversial. METHODS: A total of 174 patients underwent resections for aerodigestive tract invasion from
differentiated thyroid cancer (103 patients), medullary thyroid cancer (40 patients), and undifferentiated thyroid
cancers/unusual thyroid neoplasms (31 patients). In all, 82 patients submitted to transmural resections (window
resection, sleeve resection, or cervical evisceration), 65 patients underwent nontransmural resections (shaving
or extramucosal esophageal resections), and 27 patients had grossly incomplete resections. The measures of
outcome included surgical morbidity, locoregional recurrence, and disease-specific survival. RESULTS: Surgical
morbidity was 38% after transmural and 25% after nontransmural resection (P = .02). On histopathologic
examination, surgical margins were microscopically involved in 9% of patients after transmural and 23% of
patients after nontransmural resection (P = .014). At a mean follow-up of 35.3 months, locoregional recurrence
developed in 10 (46%) of 22 patients with microscopically incomplete and 18 (15%) of 121 patients with
microscopically complete resection (P = .001). After grossly complete resection, the mean disease-specific
survival was 101.2, 69.8, and 25.5 months for differentiated thyroid cancer, medullary thyroid cancer, and
undifferentiated thyroid cancer/unusual neoplasms, respectively (P < .001). This outcome was independent of
the type of resection. CONCLUSION: The type of cancer and resection are key determinants of outcome among
thyroid cancer patients with aerodigestive tract invasion.
PubMed-ID: 21134559

Effect of the Bethesda System for Reporting Thyroid Cytopathology on Thyroidectomy Rates and
Malignancy Risk in Cytologically Indeterminate Lesions.
Surgery, 148(6):1267-72.
Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE. 2010.
BACKGROUND: Cytologically indeterminate thyroid nodules represent a diagnostic and therapeutic challenge.
In 2007, the National Cancer Institute recommended The Bethesda System for Reporting Thyroid Cytopathology
(TBSRTC) as a means of improving the accuracy of thyroid cytopathology. Our objective was to determine the
effect of TBSRTC on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions. METHODS:
We compared thyroidectomy rates and malignancy risk in patients with indeterminate thyroid cytopathology
across 2 time periods, spanning January 2000 and November 2009; pre-TBSRTC (January 2000 to September
2003) and post-TBSRTC (June 2008 to November 2009). Statistical comparisons were performed using the
Fisher's exact test and chi-square analysis (P = .05 significant). RESULTS: We performed 938 fine-needle
aspirations in the first period, 765 in the second. We identified 78 (8.3%) cytologically indeterminate lesions in
the pre-TBSRTC group and 91 (11.9%) lesions in the post-TBSRTC group. We found no difference in
thyroidectomy rates between the groups (37/78 [47%] pre-Bethesda versus 32/91 [35%] post-Bethesda; P =
.12). However, the malignancy rate was significantly lower in the post-TBSRTC group (13/37 [35%] pre-
Bethesda versus 4/32 [13%] post-Bethesda; P = .02). CONCLUSION: Application of TBSRTC is associated with
lower malignancy risk in indeterminate thyroid nodules, despite similar thyroidectomy rates. These findings imply
that standardization of cytologic classification improves diagnostic accuracy.
PubMed-ID: 21134560

Routine Second-Opinion Cytopathology Review of Thyroid Fine Needle Aspiration Biopsies Reduces
Diagnostic Thyroidectomy.
Surgery, 148(6):1294-9.
Davidov T, Trooskin SZ, Shanker BA, Yip D, Eng O, Crystal J, Hu J, Chernyavsky VS, Deen MF, May M,
Artymyshyn RL. 2010.
BACKGROUND: Follicular thyroid carcinoma cannot be distinguished reliably from benign follicular neoplasia by
fine needle aspiration (FNA) biopsy. Given an estimated 20% risk of malignancy, many patients with
indeterminate FNA biopsies require thyroidectomy for diagnosis. Some centers have shown significant
discordance when a second pathologist evaluates the same FNA biopsy. We sought to determine whether
routine second-opinion cytopathology reduces the need for diagnostic thyroidectomy, especially in patients with

ESES Review of Recently Published Literature 2010-3                                                Page 37 of 68
indeterminate FNA biopsies. METHODS: In all, 331 thyroid FNA biopsy specimens obtained from outside
centers from 2004 to 2009 were reviewed at our institution. The FNA biopsy results were categorized into
nondiagnostic (Bethesda I), benign (Bethesda II), indeterminate (follicular/Hurthle cell neoplasm,
follicular/Hurthle cell lesion; Bethesda III & IV), and malignant (papillary or suspicious for papillary or other
malignancy; Bethesda V and VI). Second-opinion cytology was compared with the initial opinion in 331 cases
and with final operative pathology in the 250 patients who progressed to thyroidectomy. RESULTS: The average
patient age was 51 with a predominant number of female (79%) participants. The overall cytology concordance
for all 331 FNA biopsies was 66% (218/331). Concordance was highest at 86% (74/86) with malignant FNA
biopsies. Concordance in the 129 patients with indeterminate FNA biopsies was only 37% (48/129).
Indeterminate FNA biopsies were reread as nondiagnostic in 21% (27/129) of patients and as benign in 42%
(54/129) of patients. Twenty-two patients with an indeterminate FNA biopsy reread as benign progressed to
operative therapy for reasons other than cytology (eg, symptomatic nodule and radiation exposure/high risk) and
were found to be benign in 95% (21/22) of patients on operative pathology for a 95% negative predictive value.
An additional 11 patients with an indeterminate FNA reread as benign had follow-up FNA biopsies, each of
which was benign. Indeterminate FNA biopsies on initial cytology had a malignancy rate of 13% (17/129) on
operative pathology compared with 29% (14/48) for indeterminate FNA biopsies from second opinion. A second
opinion improved FNA biopsy accuracy from 60% to 74%. Overall, second-opinion cytology of indeterminate
FNA biopsies avoided diagnostic operation in 25% (32/129). CONCLUSION: Routine second opinion review of
indeterminate thyroid FNA biopsies can potentially obviate the need for diagnostic thyroidectomy in 25% of
patients without increases in false negatives.
PubMed-ID: 21134564

Do the Recent American Thyroid Association (ATA) Guidelines Accurately Guide the Timing of
Prophylactic Thyroidectomy in MEN2A?
Surgery, 148(6):1302-9.
Grubbs EG, Waguespack SG, Rich TA, Xing Y, Ying AK, Evans DB, Lee JE, Perrier ND. 2010.
BACKGROUND: In 2009, the American Thyroid Association (ATA) published consensus guidelines for timing of
prophylactic thyroidectomy (PrThy) for treatment of hereditary medullary thyroid cancer (MTC). The aim of this
study was to assess whether the clinical guidelines outlined in the ATA recommendations added to the specific
mutation risk level could predict the presence of MTC on final pathology. METHODS: A retrospective study was
performed of patients undergoing PrThy. We evaluated mutation-based risk levels in combination with 2009 ATA
guidelines for resection. RESULTS: Overall, 54 patients underwent PrThy between 1972 and 2009. The median
age at PrThy was 11.5 years (range, 2-68). Only 4 patients (8%) underwent PrThy prior to age 5 years. Most
patients with MTC (16/22, 73%) had a level C mutation, and the youngest age of MTC in a level C mutation
carrier was 5 years. The youngest age of MTC in level A or B carriers was 15 years. The single factor that
predicted an overall decreased risk of MTC at the time of PrThy was meeting all ATA mutation-based
postponement guidelines for surgical intervention (P = .04). CONCLUSION: ATA guidelines that includes risk
assessment of RET mutation are important in predicting the presence of MTC in patients who are candidates for
prophylactic thyroidectomy and in determining the timing of operative resection.
PubMed-ID: 21134565

'Ad Hoc' Sternal-Split Safely Replaces Full Sternotomy for Thyroidectomy Requiring Thoracic Access.
Am Surg, 76(11):1240-3.
Pata G, Casella C, Benvenuti M, Crea N, Di BE, Salerni B. 2010.
Mediastinal goiter (MG) removal occasionally needs sternotomy, mainly in case of subaortic extension. We
aimed to test the hypothesis that sternal-split may safely replace full sternotomy for MG removal (through total
thyroidectomy) when thoracic access is required. We conducted a prospective observational cohort study
comparing 15 subaortic MGs receiving sternal-split with 87 MGs undergoing cervicotomy alone between January
1997 and June 2009. Among 15 cases requiring sternal incision, sternal-split was extended to the angle of Louis
in nine patients (60%), to the third intercostal space (IS) in one of five (20%) cases of MGs with anterior
mediastinum involvement, and in five of 10 (50%) cases with posterior involvement (P = 0.6). Full sternotomy
was never necessary. The median hospitalization was 5 days (range, 4-8 days) after sternal access as
compared with 3 days (range, 2-4 days) after cervicotomy (P = 0.04). Complications were similar in these two
study groups: one postoperative bleeding in each group and three recurrent laryngeal nerve palsies after
cervicotomy (P = 0.5). There was no operative mortality, blood transfusion, tracheotomy requirement, wound
infection, or persistent hypoparathyroidism. Proper extension of sternal-split to the second or third IS allows an
adequate approach to both the anterior and to the posterior mediastinum, thus permitting safe management of

ESES Review of Recently Published Literature 2010-3                                                Page 38 of 68
MGs requiring thoracic access.
PubMed-ID: 21140692

Papillary Thyroid Carcinoma After Chemotherapy for Hodgkin's Disease.
Am Surg, 76(11):1316-7.
Abboud B, Yazbeck T, Daher R, Chahine G, Ghorra C. 2010.
PubMed-ID: 21140714

Thyroid Cancer Incidence Patterns in the United States by Histologic Type, 1992-2006.
Thyroid, 21(2):125-34.
schebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. 2011.
BACKGROUND: The increasing incidence of thyroid cancer in the United States is well documented. In this
study, we assessed the incidence patterns by histologic type according to demographic and tumor
characteristics to further our understanding of these cancers. METHODS: We used the National Cancer
Institute's Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed during 1992-2006
to investigate patterns for the four major histologic types of thyroid cancer by gender, race/ethnicity, and age as
well as registry, tumor stage, and size. RESULTS: Among women, papillary thyroid cancer rates were highest
among Asians (10.96 per 100,000 woman-years) and lowest among blacks (4.90 per 100,000 woman-years);
follicular cancer rates did not vary substantially by race/ethnicity (p-values >0.05), medullary cancer rates were
highest among Hispanics (0.21 per 100,000 woman-years) and whites (0.22 per 100,000 woman-years), and
anaplastic rates were highest among Hispanics (0.17 per 100,000 woman-years). Among men, both papillary
and follicular thyroid cancer rates were highest among whites (3.58 and 0.58 per 100,000 man-years,
respectively), medullary cancer rates were highest among Hispanics (0.18 per 100,000 man-years), and
anaplastic rates were highest among Asians (0.11 per 100,000 man-years). Racial/ethnic-specific rates did not
vary notably across registries. In contrast to age-specific rates of papillary thyroid cancer that peaked in midlife
(age 50), especially pronounced among women, rates for follicular, medullary, and anaplastic types continued to
rise across virtually the entire age range, especially for anaplastic carcinomas. Female-to-male incidence rate
ratios among whites decreased with age most steeply for the follicular type and least steeply for the medullary
type; it was <1 until the very oldest ages for the anaplastic type. CONCLUSION: We conclude that the similar
age-specific patterns and lack of geographical variation across the SEER racial/ethnic groups indicate that
detection effects cannot completely explain the observed thyroid cancer incidence patterns as variation in the
amount or quality of healthcare provided has been shown to vary by SEER racial/ethnic groups, gender, and
age. We find that the variations in age-specific patterns by gender and across histologic types are intriguing and
recommend that future etiologic investigation focus on exogenous and endogenous exposures that are
experienced similarly by racial/ethnic groups, more strongly among women, and distinctively by age.
PubMed-ID: 21186939

Prevalence, Clinicopathologic Features, and Somatic Genetic Mutation Profile in Familial Versus
Sporadic Nonmedullary Thyroid Cancer.
Moses W, Weng J, Kebebew E. 2010.
Background: Although hereditary nonmedullary thyroid cancer is recognized as a distinct and isolated familial
syndrome, the precise prevalence and genetic basis are poorly understood. Moreover, whether familial
nonmedullary thyroid cancer (FNMTC) has a more aggressive clinical behavior is controversial. The objectives of
this study were to determine the prevalence of FNMTC, and compare the extent of disease and tumor somatic
genetic alteration in patients with familial and sporadic papillary thyroid cancer. Methods: The main study entry
criterion was patients who had a thyroid nodule that required a clinical evaluation with fine-needle aspiration
biopsy and or thyroidectomy. A family history questionnaire was used to determine the presence of familial and
sporadic thyroid cancer. Thyroid nodule fine-needle aspiration biopsy samples and tumor tissue at the time of
thyroidectomy were used to test for somatic genetic mutations (BRAF V600E, NRAS, KRAS, NTRK1,
RET/PTC1, and RET/PTC3). Results: There were 402 patients with 509 thyroid nodules enrolled in the study.
The prevalence of FNMTC was 8.8% in all patients with thyroid cancer and 9.4% in patients with only papillary
thyroid cancer. None of the patients with FNMTC had another familial cancer syndrome. There was no
significant difference in gender, tumor size, lymph node metastasis, and overall stage between sporadic and
familial cases of thyroid cancer. Patients with FNMTC were younger at diagnosis than patients with sporadic
papillary thyroid cancer (p < 0.002). Seventy-nine of the 504 thyroid nodules had somatic genetic mutations (29
BRAF V600E, 29 NRAS, 8 KRAS, 1 NTRK1, 4 RET/PTC1, and 8 RET/PTC3). There was no significant
difference in the number or type of somatic mutations between sporadic and hereditary cases of papillary thyroid

ESES Review of Recently Published Literature 2010-3                                                  Page 39 of 68
cancer. Conclusions: We found a higher prevalence of FNMTC in patients with papillary thyroid cancer than
previously reported. Patients with FNMTC present at a younger age. Somatic mutations and extent of disease
are similar in sporadic and FNMTC cases.
PubMed-ID: 21190444

Normal Parathyroid Hormone Levels Do Not Exclude Permanent Hypoparathyroidism After
Thyroid, 21(2):145-50.
Promberger R, Ott J, Kober F, Karik M, Freissmuth M, Hermann M. 2011.
BACKGROUND: Permanent hypoparathyroidism has become the most common and the most severe
complication after thyroid surgery. In our experience, some patients suffer from permanent hypocalcemia and
related symptoms despite normal parathyroid hormone (PTH) values after thyroid surgery. The aim of this work
was to present a series of such patients with long-term hypocalcemia and normal PTH values to evaluate to
what extent parathyroid function was impaired by thyroidectomy, and determine whether irregularities of bone
and calcium metabolism were associated with this phenomenon. METHODS: We present a series of eight
patients with normal PTH and subnormal calcium levels at follow-up 2 months after thyroid surgery. Outcome
parameters were intra- and postoperative PTH and calcium kinetics, and the following markers of calcium and
bone metabolism at long-term follow-up: serum calcium, total serum albumin, ionized calcium, magnesium, PTH,
25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, urinary calcium, urinary creatinine, osteocalcin, c-terminal
telopeptide of type I collagen, and alkaline phosphatase. RESULTS: All patients had normal calcium and PTH
levels at the start of the operation. The intraoperative decline in PTH was >90%; the trough (3.3% of
preoperative value) was reached 3 hours after surgery. Patients underwent complete determination of bone
metabolism parameters during long-term follow-up 13.8 +/- 2.4 months after surgery. Hypocalcemia was found in
all eight patients, as well as PTH levels within the normal range. In three patients (3/8 = 37.5%), none of the
other parameters was altered. In the remaining five patients, only isolated abnormalities in bone and calcium
metabolism parameters were found (i.e., alterations in urinary calcium, thyrotropin, 25-hydroxyvitamin D,
osteocalcin, and c-terminal telopeptide of type I collagen). CONCLUSIONS: An intraoperative injury to the
parathyroid glands or their vascularization is the likely contributing factor to the development of permanent
hypocalcemia with normal PTH values after thyroid surgery. The remaining parathyroid tissue is subject to a
maximum stimulus by hypocalcemia and, therefore, is able to maintain PTH values in the normal range. These
are still too low to re-establish normal serum calcium levels. In these patients, the term "hypoparathyroidism"
might be replaced with "parathyroid insufficiency.".
PubMed-ID: 21190447

Thyroid Pathology in PTEN-Hamartoma Tumor Syndrome: Characteristic Findings of a Distinct Entity.
Thyroid, 21(2):135-44.
Laury AR, Bongiovanni M, Tille JC, Kozakewich H, Nose V. 2011.
BACKGROUND: Phosphatase and tensin homolog deleted on chromosome ten (PTEN)-hamartoma tumor
syndrome (PHTS) is a complex disorder caused by germline inactivating mutations of the PTEN tumor
suppressor gene. PHTS includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and
Proteus-like syndromes. Affected individuals develop both benign and malignant tumors in a variety of tissues,
including the thyroid. This study is to better characterize and describe the thyroid pathology within the different
entities of this syndrome, and examine whether there is an association between specific thyroid findings and
different PTEN mutations. METHODS: Twenty patients with known PTEN mutations, and/or clinical diagnosis of
PHTS, and thyroid pathology were identified: 14 with CS and 6 with BRRS. RESULTS: Thyroid pathology
findings were as follows: multiple adenomatous nodules in a background of lymphocytic thyroiditis (LT) in 75%,
papillary carcinoma in 60%, LT alone in 55%, follicular carcinoma in 45%, C-cell hyperplasia in 55%, and
follicular adenomas in 25%. Within the papillary carcinoma group, there were 6 microcarcinomas, 5 follicular
variants, and 1 classical type. CONCLUSIONS: There were no morphologic differences between the thyroid
findings in CS and BRRS. Also, there was no correlation between specific PTEN germline mutations (exons 5, 6,
and 8) and pathologic findings. Distinctive and characteristic findings in PHTS include multiple unique
adenomatous nodules in a background of LT, and C-cell hyperplasia; it is vital that pathologists recognize the
classical histologic features of this syndrome to alert clinicians to the possibility of this syndrome in their patients.
PubMed-ID: 21190448

ESES Review of Recently Published Literature 2010-3                                                      Page 40 of 68
- None -

Randomized controlled trials
- None -

Other Articles
Remedial Operation for Primary Hyperparathyroidism.
World J Surg, 33(11):2324-34.
Prescott JD, Udelsman R. 2009.
BACKGROUND: Remedial surgery for patients with persistent or recurrent primary hyperparathyroidism (1
degrees HPT) remains a significant challenge. Cervical reexploration is technically difficult; reoperative neck
anatomy is distorted by fibrosis and, as a result, remedial 1 degrees HPT patients carry an increased risk of
injury to the recurrent (RLN) and superior laryngeal nerve(s) as well as to normal residual parathyroid tissue.
Causative hyperfunctioning parathyroid tissue is also more frequently ectopic in the remedial setting and can
thus be difficult to localize. METHODS: This report assimilates the current data underlying preoperative,
intraoperative and postoperative remedial 1 degrees HPT management and presents an evidence-based
algorithm for the management of remedial parathyroid disease. Recommendations are graded according to the
quality of supporting data using the system initially developed by Sackett (Chest 95:2S-4S, 1989) and
subsequently modified by Heinrich et al. (Ann Surg 243:154-168, 2006). RESULTS: Recent advances in
preoperative localization and intraoperative adjuncts have lead to substantial improvements in outcomes after
remedial surgery. Preoperative localization techniques, including sestamibi scintigraphy (MIBI), high resolution
ultrasound (US), US-guided fine needle aspiration (FNA) and selective venous sampling (SVS), coupled with
intraoperative adjuncts such as the rapid parathyroid hormone (PTH) assay have lead to reoperative cure rates
as high as 96 percent. Nonetheless, management of remedial 1 degrees HPT varies significantly between
surgeons and no formal recommendations standardizing the care of these patients have been published.
CONCLUSIONS: Despite the significant challenges associated with remedial surgery for 1 degrees HPT,
excellent outcomes can be reproducibly achieved when proper pre-, intra-, and postoperative management is
PubMed-ID: 19290572

Ectopic Parathyroid Adenoma Located Inside the Hypoglossal Nerve.
Head Neck, 32(9):1273-6.
Karvounaris DC, Symeonidis N, Triantafyllou A, Flaris N, Sakadamis A. 2010.
BACKGROUND: Intraneural parathyroid adenomas are extremely rare, with only 9 cases of intravagal
adenomas reported. We report the first case of an ectopic parathyroid adenoma located within the hypoglossal
nerve. METHODS AND RESULTS: A 62-year-old woman presented with a palpable nodule in the right
submandibular area, reduced bone mass, and elevated calcium and parathormone levels. Preoperative
investigation with neck ultrasound and MRI did not provide a definitive diagnosis, whereas sestamibi scan
showed slightly increased radiotracer accumulation in the same area. Intraoperatively, the right hypoglossal
nerve was found to course through the lesion and, despite the attempt to salvage it, most of its fibers were
transected. Histopathology confirmed the presence of a parathyroid adenoma inside the trunk of a nerve.
Postoperatively, calcium and parathormone levels decreased but right hypoglossal nerve paresis was noted.
CONCLUSION: This unique case emphasizes the variability of parathyroid anatomy and the difficulties faced by
the surgeon when treating this disease process.
PubMed-ID: 19691113

Usefulness of Intraoperative Parathyroid Hormone Measurements in Patients With Renal
Head Neck, 32(10):1328-35.
Freriks K, Hermus AR, de Sevaux RG, Bonenkamp HJ, Biert J, den HM, Sweep FC, van Hamersvelt HW. 2010.

ESES Review of Recently Published Literature 2010-3                                               Page 41 of 68
BACKGROUND: In renal hyperparathyroidism, it remains unclear whether intraoperative parathyroid hormone
(PTH) measurements can predict postoperative outcome and guide the extent of surgical exploration.
METHODS: In 42 parathyroidectomies for renal hyperparathyroidism, we analyzed the predictive value of the
Miami Criterion of 50% intraoperative PTH decrease. We used receiver operating characteristic (ROC) curves to
find the criterion with the best diagnostic performance. We also investigated whether the whole PTH assay
improved accuracy. RESULTS: Twenty-six operations (62%) resulted in normal postoperative PTH. With the
Miami Criterion, cure was predicted with a sensitivity of 95% and specificity of only 8%. Specificity could be
improved to 50% using a 70% PTH decrease as cut-off level. The whole PTH assay did not improve accuracy.
CONCLUSION: Prediction of cure after parathyroidectomy for renal hyperparathyroidism might be improved with
a criterion of 70% PTH decrease 10 minutes after excision of all parathyroid glands. Prospective analysis needs
to validate this new criterion.
PubMed-ID: 20091683

Usefulness of the Combination of Ultrasonography and 99mTc-Sestamibi Scintigraphy in the
Preoperative Evaluation of Uremic Secondary Hyperparathyroidism.
Head Neck, 32(9):1226-35.
Vulpio C, Bossola M, De GA, Maresca G, Bruno I, Fadda G, Morassi F, Magalini SC, Giordano A, Castagneto M.
BACKGROUND: The usefulness of the combination of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI)
parathyroid scintigraphy and ultrasonography to detect parathyroid glands (PTGs) in secondary
hyperparathyroidism (SHPT) is still controversial. METHODS: In all, 21 patients with SHPT underwent
parathyroidectomy. The sensitivity and specificity of ultrasonography and scintigraphy related to site, size,
hyperplasia type of PTG, concomitant thyroid disease, and the frequency of intraoperative frozen sections were
determined. RESULTS: The sensitivities of scintigraphy and ultrasonography were 62% and 55%, and the
specificity was 95% for both procedures. The sensitivity of combined techniques was 73%. The scintigraphy
detected 7/9 (78%) ectopic PTGs, whereas ultrasonography was always negative. A PTG maximum longitudinal
diameter <8 mm, the presence of diffuse hyperplasia, the upper localization of glands, and the presence of
concomitant thyroid disease reduced the sensitivity and specificity of imaging techniques. In cases of positive
imaging, the rate of intraoperative frozen sections was significantly lower. CONCLUSIONS: The ultrasonography
and sestamibi scintigraphy, which showed a higher sensitivity than that of either ultrasonography or scintigraphy
alone, led to a reduction of intraoperative frozen sections and to preoperative diagnosis of ectopic (29%) or
supernumerary PTGs (10%) and concomitant nodular thyroid disease (24%).
PubMed-ID: 20091692

The Surgical Strategy and the Molecular Analysis of Patients With Parathyroid Cancer.
World J Surg, 34(11):2604-10.
Enomoto K, Uchino S, Ito A, Watanabe S, Shibuya H, Enomoto Y, Noguchi S. 2010.
BACKGROUND: Parathyroid cancer is a rare endocrine tumor, and the prognostic factors for this cancer remain
unclear. The standard therapy is en bloc resection of the primary tumor at the time of the initial operation.
However, the clinical significance of prophylactic neck dissection (PND) in the management of parathyroid
cancer has not yet been established. In this study, we investigated its clinical significance in patients with
parathyroid cancer and the association of gene mutations with tumor progression. METHODS: A total of 12
patients with parathyroid cancer were treated and have been followed at Noguchi Thyroid Clinic and Hospital
Foundation since 1977. In all, 11 patients were treated with the initial surgery for the cancer, and 1 patient
underwent surgery for a metastatic lung lesion. Somatic and germ-line mutations of the HRPT2 and MEN1 were
examined by polymerase chain reaction and automated DNA sequencing. RESULTS: En bloc resections of
thyroid tissue were performed in 10 patients, and 1 patient underwent only parathyroidectomy with limited
resection of the thyroid gland. PND was performed in eight patients, and no lymph node metastases were found
in the histological specimens. Six of the eight patients had no evidence of the disease, and two had recurring
disease (neck lymph node and lung in one patient and local, lung, and brain in another). PND was not performed
in three patients, two of whom had no evidence of the disease and one with recurrence at the site of a regional
lymph node. There were no significant differences in disease-free survival and cause-specific survival between
the patients who underwent PND and the patients who did not (P = 0.98 and P = 0.32, respectively). Among the
12 patients with parathyroid cancer, 1 had a germ-line mutation of the HRPT2 at exon 7, codon 234, CGA (Arg)
to TGA (Stop), and 1 patient had a tumor-specific mutation at exon 1, nucleotide 34-37 delAACA. Two of the four
patients with recurrent disease had an HRPT2 gene mutation. MEN1 gene analysis revealed one somatic
missense mutation at exon 2, codon 121, GTC (Val) to GAC (Asp) in one patient. CONCLUSIONS: PND for

ESES Review of Recently Published Literature 2010-3                                               Page 42 of 68
patients with parathyroid cancer resulted in no evidence of lymph node metastasis and does not improve the
prognosis. HRPT2 gene mutation may be associated with tumor recurrence.
PubMed-ID: 20480190

Validity and Limits of Intraoperative Parathyroid Hormone Monitoring During Minimally Invasive
Parathyroidectomy: a 10-Year Experience.
Surg Endosc, 24(12):3156-60.
Ozimek A, Gallwas J, Stocker U, Mussack T, Hallfeldt KK, Ladurner R. 2010.
BACKGROUND: The availability of intraoperative intact parathyroid hormone monitoring allows the success of
minimally invasive parathyroidectomy to be ensured during the operation. However, false-negative results
leading to unnecessary explorations and difficulties in interpreting the data raise concern about the effectiveness
of the method. METHODS: Patients with primary hyperparathyroidism (pHPT) and one unequivocally enlarged
parathyroid gland on preoperative ultrasound or (99m)Tc-SestaMIBI scintigraphy underwent minimally invasive
video-assisted parathyroidectomy according to the technique initially described by Miccoli. Intraoperatively, rapid
electrochemiluminescence immunoassay was used to measure intact parathyroid hormone (iPTH) levels before
the operation, after complete mobilization of the adenoma (preexcision value), and 5, 10, and 15 min after the
excision. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels
and subsequent attainment of the normal range within 15 min were observed. RESULTS: Between November
1999 and November 2009, 235 (43%) of 546 patients with pHPT were eligible for a minimally invasive approach.
Intraoperative iPTH monitoring showed 221 true-positive, 1 false-positive, 6 false-negative, and 7 true-negative
results. This calculated to a sensitivity of 97% and a specificity of 88%. CONCLUSIONS: Despite the availability
of high-resolution ultrasound and (99m)Tc-SestaMIBI scintigraphy, the presence of multiple glandular disease
cannot be ruled out completely. Although the authors observed six false-negative results, they believe that
intraoperative iPTH monitoring represents a valuable asset for minimally invasive parathyroidectomy because it
identifies sporadic hyperplasia.
PubMed-ID: 20490562

Fluorescence-Guided Minimally Invasive Parathyroidectomy: Clinical Experience With a Novel
Intraoperative Detection Technique for Parathyroid Glands.
World J Surg, 34(9):2217-22.
Prosst RL, Weiss J, Hupp L, Willeke F, Post S. 2010.
BACKGROUND: Detection of normal and pathologic parathyroid glands often is difficult due to their variability in
number and location. We have implemented photosensitizer-induced fluorescence for the routine intraoperative
identification of parathyroids for the surgical treatment of hyperparathyroidism. METHODS: From 2004 to 2007,
25 patients suffering from primary and secondary hyperparathyroidism underwent minimally invasive
videoscopic-assisted parathyroidectomy after oral photosensitization with aminolevulinic acid (ALA). RESULTS:
Fluorescence was sufficiently strong in 48% of patients to aid faster detection of the glands in situ. In an
additional 44%, the fluorescence behavior supported the identification of the glands in situ and after excision,
yielding a total of 92% of glands whose identity could be confirmed by the fluorescence technique.
CONCLUSIONS: Fluorescence-guided minimally invasive parathyroidectomy is technically feasible and may
support the surgeon in detecting and confirming the parathyroid glands. As the fluorescence method requires
only moderate additional technical efforts and clinical expenditure, it is a valuable add-on component in
parathyroid surgery to facilitate the operation.
PubMed-ID: 20512496

25-Hydroxyvitamin D Status Does Not Affect Intraoperative Parathyroid Hormone Dynamics in Patients
With Primary Hyperparathyroidism.
Ann Surg Oncol, 17(11):2958-62.
Adler JT, Sippel RS, Chen H. 2010.
BACKGROUND: Deficiency of 25-hydroxyvitamin D (25OHD) is a stimulus for the secretion of parathyroid
hormone (PTH). During surgery for primary hyperparathyroidism, 25OHD deficiency may artificially elevate PTH,
decreasing the sensitivity of intraoperative PTH (ioPTH) measurements. MATERIALS AND METHODS: Of 351
patients with known 25OHD status who underwent curative surgical treatment of primary hyperparathyroidism,
198 (56%) patients were 25OHD deficient (<25 ng/mL). A curative decrease in ioPTH was defined as a greater
than 50% PTH decrease 5, 10, or 15 min after resection. RESULTS: There was no statistical difference between
25OHD deficient and sufficient patients in PTH, phosphorous, and alkaline phosphatase preoperatively. There

ESES Review of Recently Published Literature 2010-3                                                 Page 43 of 68
was a positive correlation between PTH and calcium, alkaline phosphatase, and gland weight, while there was
an inverse correlation between preoperative PTH and 25OHD. The average ioPTH decrease was not
significantly different after 5, 10, or 15 min, and 25OHD status did not affect when ioPTH indicated surgical cure.
CONCLUSIONS: Lower 25OHD levels are correlated with higher PTH and alkaline phosphatase levels in
patients with primary hyperparathyroidism. 25OHD status did not affect the average percent ioPTH decrease or
the rate of cure. 25OHD deficiency does not affect ioPTH dynamics.
PubMed-ID: 20544293

Prospective Evaluation of the Rate and Impact of Hemolysis on Intraoperative Parathyroid Hormone
(IOPTH) Assay Results.
 Ann Surg Oncol, 17(11):2963-9.
Moalem J, Ruan DT, Farkas RL, Shen WT, Miller S, Duh QY, Clark OH, Kebebew E. 2010.
BACKGROUND: Intraoperative parathyroid hormone (IOPTH) is commonly used during minimally invasive
parathyroidectomy. Retrospective evidence suggested that hemolysis may artificially lower IOPTH results.
Falsely decreased IOPTH measurements could result in either failed parathyroidectomy or unnecessary bilateral
neck exploration. METHODS: A total of 130 IOPTH specimens from 30 patients were assayed before and after
induction of mechanical hemolysis using a vortex and inert sterile glass beads. Free hemoglobin (Hg) was
measured as a surrogate for extent of hemolysis. Paired sample t test was used for comparison of matched
prehemolysis and posthemolysis specimens. RESULTS: Of the samples, 16.9% were hemolyzed at the baseline
(11 of 72 pre-excision, 11 of 55 postexcision). We successfully induced moderate hemolysis (DeltaHg 0.1-1.0
mg/DL) in 66 samples that had minimal hemolysis at baseline. In these, mechanical hemolysis increased free Hg
by an average of 0.37 mg/DL (533%; mean posthemolysis free Hg = 0.43; moderate hemolysis) and lowered
PTH values by an average of 39% (median = 36%, SD = 11%; P = .002). The decrease in PTH was related to
the extent of hemolysis induced (r = 0.51; P < .001), but was unrelated to the specimen's baseline (true) PTH (P
= .24). In 12 of 30 patients, the experimentally hemolyzed pre-excision PTH value would have reduced the 50%
threshold sufficiently to cause a false-negative result. In 6 of the 30 parathyroidectomies, a hemolyzed
postexcision PTH value would have decreased PTH value sufficiently to cause a false-positive result.
CONCLUSIONS: Hemolysis of IOPTH specimens occurs commonly and falsely reduces PTH results. In 18 of 30
patients, this effect was sufficient to have contributed to either a false-positive or false-negative IOPTH result.
PubMed-ID: 20552403

Long-Term Symptom Relief From Primary Hyperparathyroidism Following Minimally Invasive
World J Surg, 34(9):2223-7.
Aspinall SR, Boase S, Malycha P. 2010.
BACKGROUND: The affect of the surgical approach for primary hyperparathyroidism (1HPT) on long-term
symptom relief has not been studied. This study compares the long-term relief of symptoms assessed by the
Parathyroidectomy Assessment of Symptoms (PAS) score in patients undergoing bilateral neck exploration
(BNE) and minimally invasive parathyroidectomy (MIP). METHODS: In this case-control study, patients with
1HPT who had followed a protocol to assess symptoms before and after parathyroid surgery between 1999 and
2008 were contacted by letter and had blood taken to assess calcium, ionized calcium, and parathyroid hormone
(PTH). The main aim was to assess symptoms at long-term follow-up using the PAS score. The incidence of
persistent or recurrent 1HPT at long-term follow-up after MIP and BNE was also compared. RESULTS: Two
hundred and forty-six patients underwent parathyroid surgery and 142 responded to our correspondence, of
which 64 underwent MIP and 78 BNE. Follow-up after BNE was longer than MIP (61 vs. 41 months). At long-
term follow-up, the mean PAS score fell by 125 and 175 in the MIP and BNE groups, respectively. There was no
statistically significant difference in the decline of the PAS score between the MIP and BNE groups. Six patients
developed persistent or recurrent 1HPT following MIP compared to three after BNE; this difference was not
statistically significant. CONCLUSIONS: This study is the first to report on long-term symptom relief from 1HPT
after MIP, and demonstrates that both MIP and BNE can achieve this. In order to establish whether the long-
term outcomes from these procedures are equivalent, further adequately powered studies are required.
PubMed-ID: 20556605

Video-Assisted Bilateral Neck Exploration in Patients With Primary Hyperparathyroidism and Failed
Localization Studies.
World J Surg, 34(10):2344-9.

ESES Review of Recently Published Literature 2010-3                                                 Page 44 of 68
Alesina PF, Singaporewalla RM, Walz MK. 2010.
BACKGROUND: In primary hyperparathyroidism (pHPT) positive preoperative localization studies are accepted
as a precondition for applying minimally invasive surgical techniques. Without localization, open bilateral neck
exploration (BNE) is considered the standard option. The present study analyzes the feasibility and effectiveness
of minimally invasive video-assisted BNE in patients with pHPT and negative or discordant localization studies.
METHODS: From a prospective series of 380 minimally invasive video-assisted parathyroidectomies (MIVAP)
performed in 367 patients for pHPT (1999-2009), 68 patients (10 male, 58 female; mean age: 58 years) were
selected. These patients had failed localization studies and underwent BNE with the MIVAP technique.
Operative time, complications, conversions to open technique, and cure rate were determined. RESULTS: Mean
operative time was 52 +/- 26 min (range: 20-180 min). MIVAP with BNE was successfully completed in 66 (97%)
patients with two conversions to open technique. Recurrent laryngeal nerve palsy occurred in one patient.
Biochemical cure was achieved in 67 patients (98.5%), in 65 patients (95.5%) after the first operation and in two
more patients by video-assisted re-exploration on the first postoperative day. One patient remained with
persistent disease even after repeated open BNE. CONCLUSIONS: In experienced hands, video-assisted BNE
with the MIVAP technique, for pHPT and failed localization studies, is feasible, safe, and gives results equivalent
to the conventional open technique.
PubMed-ID: 20596707

Underutilization of Parathyroidectomy in Elderly Patients With Primary Hyperparathyroidism.
J Clin Endocrinol Metab, 95(9):4324-30.
Wu B, Haigh PI, Hwang R, Ituarte PH, Liu IL, Hahn TJ, Yeh MW. 2010.
CONTEXT: Primary hyperparathyroidism (PHPT) disproportionately affects older patients, who may face higher
thresholds for surgical intervention compared to young patients. OBJECTIVE: The aim was to examine for
differences in the utilization of parathyroidectomy attributable to age. DESIGN: We conducted a retrospective
cohort study. PARTICIPANTS: Patients with biochemically diagnosed PHPT during the years 1995-2008 were
identified within an integrated health care delivery system in Southern California encompassing approximately 3
million individuals. MAIN OUTCOME MEASURES: The outcome measures were parathyroidectomy (PTx) and
time interval to surgery. RESULTS: We found 3388 patients with PHPT, 964 (28%) of whom underwent PTx.
Patients aged 60+ yr comprised 60% of the study cohort. The likelihood of PTx decreased linearly among
patients aged 60+ when compared to patients aged 50-59, an effect that persisted in multivariate analysis: odds
ratio 0.68 for ages 60-69 (P < 0.05); 0.41 for ages 70-79 (P < 0.0001), and 0.11 for age 80+ (P < 0.0001). The
PTx rate for patients aged 70+ was 14%. Among patients meeting 2002 consensus criteria for surgical
treatment, 45% of those aged 60-69 and 24% of those aged 70+ underwent PTx. A Cox proportional hazards
model showed that patients aged 60+ experienced significantly longer delays from diagnosis to surgery
compared to young patients (P < 0.0001). CONCLUSIONS: PHPT is undertreated in the elderly. We observed a
progressive age-related decline in PTx rate that renders patients aged 70+ unlikely to have definitive treatment,
irrespective of comorbidity and eligibility for surgery.
PubMed-ID: 20610600

The Results of Surgery for Mediastinal Parathyroid Tumors: a Comparative Study of 63 Patients.
Langenbecks Arch Surg, 395(7):947-53.
Iacobone M, Mondi I, Viel G, Citton M, Tropea S, Frego M, Favia G. 2010.
PURPOSE: Parathyroidectomy for ectopic mediastinal hyperfunctioning glands could be performed by
transcervical approach, sternotomy, thoracotomy, and recently by thoracoscopic and mediastinoscopic
approaches. This study was aimed to analyze the results of traditional and video-assisted parathyroidectomy for
mediastinal benign hyperfunctioning glands. METHODS: Fifty-one upper mediastinal exploration by a
conventional cervicotomy, 12 by video-assisted approaches (two thoracoscopy and 10 transcervical
mediastinoscopy) and six by sternotomy were performed in 63 patients with primary hyperparathyroidism.
RESULTS: Video-assisted and sternotomic parathyroid explorations achieved biochemical cure in all cases;
following conventional transcervical mediastinal exploration, a persistent hyperparathyroidism occurred in 11.8%
of patients, who were subsequently cured by sternotomic approach. No complications occurred after video-
assisted parathyroidectomy, while an overall morbidity rate of 50% and 10% was found after sternotomic and
conventional cervicotomic approaches. Postoperative pain and hospital stay were significantly increased
following sternotomy; patient's subjective cosmetic satisfaction was significantly higher after video-assisted and
conventional cervicotomic approaches. CONCLUSIONS: Conventional cervicotomic parathyroidectomy may
achieve satisfactory results, especially for upper mediastinal glands. Sternotomic approaches are effective, but
should be limited because of invasiveness and increased morbidity. In case of deep and lower hyperfunctioning

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mediastinal parathyroids, video-assisted approaches represent a less invasive, effective, and safe alternative
and might be the technique of choice.
PubMed-ID: 20623135

Changing Biochemical Presentation of Primary Hyperparathyroidism.
Langenbecks Arch Surg, 395(7):925-8.
Almquist M, Bergenfelz A, Martensson H, Thier M, Nordenstrom E. 2010.
PURPOSE: Patients with primary hyperparathyroidism, pHPT, present with milder symptoms than previously.
Some, but not all studies, suggest that this change in clinical pattern also implies lower preoperative parathyroid
hormone (PTH) and/or calcium levels and smaller adenomas. This is important since reports indicate that
smaller adenomas are more difficult to detect on preoperative imaging, possibly increasing the risk of surgical
failure. METHODS: There were 640 patients with histologically confirmed single-gland pHPT identified in a
prospectively collected database. Median values of preoperative calcium, PTH, as well as adenoma weight were
compared in three different time periods: 1990-1995, 1996-2000, and 2000-2007. Correlation between the
preoperative levels of calcium and PTH and adenoma weight was calculated. RESULTS: Preoperative ionized
calcium decreased significantly over time (p < 0.001). There was a positive correlation between preoperative
PTH and adenoma weight (r = 0.32, p < 0.001). The magnitude of this correlation decreased over time. In
women, adenoma weight decreased significantly over time (p = 0.03). Median (25th-75th percentile) adenoma
weight in women was 750 (400-1,380) mg, 650 (350-1,205) mg, and 520 (305-1,065) mg in the first, second, and
third period, respectively. CONCLUSION: From 1990 to 2007, there was a significant trend to operate pHPT
patients with lower preoperative serum ionized calcium levels. In women, the adenoma weight decreased. This
trend could potentially lead to decreased sensitivity in preoperative localization procedures.
PubMed-ID: 20623136

Impact of Thyroid Nodular Disease on 99mTc-Sestamibi Scintigraphy in Patients With Primary
Langenbecks Arch Surg, 395(7):929-33.
Gomez-Ramirez J, Sancho-Insenser JJ, Pereira JA, Jimeno J, Munne A, Sitges-Serra A. 2010.
BACKGROUND: Primary hyperparathyroidism with coexisting thyroid nodular disease (TND) has been
considered a contraindication for selective parathyroidectomy because the low sensitivity of preoperative
localization studies, especially 99(m)Tc-sestamibi scanning (MIBI) and ultrasound. The aim of this study was to
assess the impact of concomitant TND in the preoperative image studies. METHODS: A total of 236 consecutive
patients who had parathyroidectomy for sporadic hyperparathyroidism and the preoperative localization study
that was done with MIBI were reviewed. Patients were divided into three groups: those who did not have any
thyroid disease, those who had concomitant TND not necessary to resect, and those in whom thyroid resection
due to TND was necessary at the time of parathyroidectomy. RESULTS: MIBI showed a sensitivity of 78.5% in
patients without concomitant TND, 73% in patients with TND but not thyroidectomy needed, and 54.5% in the
cases that thyroid resection was necessary. When MIBI and ultrasound were both suspicious for an adenoma,
the sensitivity was not influenced by the TND. CONCLUSION: In patients with coexisting thyroid disease but not
thyroidectomy needed, MIBI scintigraphy contributes to the detection of a solitary adenoma. When thyroid
resection is required, MIBI imaging is often negative.
PubMed-ID: 20625763

Surgery for Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism.
Br J Surg, 97(10):1528-34.
Waldmann J, Lopez CL, Langer P, Rothmund M, Bartsch DK. 2010.
BACKGROUND: Surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated primary
hyperparathyroidism (pHPT) is difficult as the condition it is caused by asymmetrical multiple gland hyperplasia.
It is uncertain which operative procedure provides the best outcome with regard to long-term normocalcaemia.
METHODS: All patients who had surgery for genetically confirmed MEN1-associated pHPT between 1987 and
2009 were identified from a prospective database. Clinical data, operative procedures and outcome were
analysed retrospectively. RESULTS: A total of 47 patients were identified. Twenty-three patients underwent total
parathyroidectomy with thymectomy and autotransplantation (TPTX + AT), 11 patients subtotal
parathyroidectomy (3-3.5 glands, SPTX) with thymectomy, and 13 patients selective gland excision (fewer than 3
glands, SGE). Rates of persistent disease, recurrent disease and permanent hypoparathyroidism after TPTX +
AT were 4 per cent (1 patient), 4 per cent (1 patient) and 22 per cent (5 patients) respectively. Respective rates

ESES Review of Recently Published Literature 2010-3                                                Page 46 of 68
after SPTX were 0 per cent, 18 per cent (2 patients) and 45 per cent (5 patients), which were not statistically
different from those following TPTX + AT. SGE resulted in persistent disease in 23 per cent (3 patients) and a
significantly higher rate of recurrent disease (46 per cent, 6 patients; P = 0.004 versus TPTX, P = 0.210 versus
SPTX), but permanent hypoparathyroidism did not occur. CONCLUSION: TPTX + AT and SPTX both seem
adequate surgical procedures for the treatment of MEN1-associated pHPT and are associated with fewer
recurrences than SGE.
PubMed-ID: 20629112

Hypoparathyroidism After Total Parathyroidectomy Plus Subcutaneous Autotransplantation for
Secondary Hyperparathyroidism--Any Side Effects?
World J Surg, 34(10):2350-4.
Chou FF, Chi SY, Hsieh KC. 2010.
BACKGROUND: This retrospective, case-control study was designed to find side effects of hypoparathyroidism
after total parathyroidectomy plus autotransplantation. METHODS: After successful total parathyroidectomy plus
autotransplantation for symptomatic secondary hyperparathyroidism, 19 patients who had intact parathyroid
hormone (iPTH) levels <10 pg/ml during the follow-up period of 1 year and 38 patients, who had levels >10
pg/ml, were enrolled as the hypoparathyroid and nonhypoparathyroid groups. Data were collected on etiology,
symptoms, serum levels of calcium, phosphate, alkaline phosphatase (Alk-ptase), iPTH, and bone mineral
density (BMD) at different sites. Then, 1 week, 3 months, and 1 year after surgery, serum levels of calcium,
phosphate, Alk-ptase, and iPTH were measured again. Three months later, symptoms were recorded. One year
after surgery, the BMD at different sites was measured again. Patients' daily requirements of calcium carbonate
and vitamin D3 were recorded at the mean follow-up of 24 months. RESULTS: Calcium, phosphate, and iPTH
levels decreased significantly 1 week, 3 months, and 1 year after surgery, and Alk-ptase levels increased at 1
week and then decreased significantly 3 months and 1 year after surgery. Symptoms improved significantly 3
months after surgery. The BMD of different sites increased significantly at 1 year. There were no differences
between the two groups regarding changes of symptoms, BMD, and calcium, phosphate, and Alk-ptase levels.
Hypoparathyroid patients required significantly more calcium carbonate and vitamin D3 than nonhypoparathyroid
patients did (P = 0.002). CONCLUSIONS: Even though hypoparathyroid patients require more calcium
carbonate and vitamin D3 than nonhypoparathyroid patients do, they do not have any side effects.
PubMed-ID: 20635084

Lymph Node Involvement and Surgical Approach in Parathyroid Cancer.
World J Surg, 34(11):2611-20.
Schulte KM, Talat N, Miell J, Moniz C, Sinha P, az-Cano S. 2010.
BACKGROUND: The best surgical approach to parathyroid cancer is disputed. Recommendations vary and are
built on incoherent evidence. High rates of recurrence and death require an in-depth review of underlying
findings. METHODS: This retrospective study includes 11 patients with parathyroid cancer who underwent
surgery with central and/or lateral neck dissection by a single surgeon between 2005 and 2010. The diagnosis
was based on histopathological criteria in all patients. Patterns of lymph node and soft tissue involvement of
these and formerly reported patients were analysed based on full-text review of all published cases of
parathyroid cancer. RESULTS: In this series only 1 of 11 patients (9.1%) manifested lymph node metastasis. In
the literature, lymph node metastases have been reported in only 6.5% of 972 published patients, or in 32.1% of
the 196 in whom lymph node involvement was assessed by the authors. They were, with few exceptions,
localised in the central compartment. Recurrence in soft tissue is more frequent than in locoregional lymph
nodes. CONCLUSION: Oncological en bloc clearance of the central compartment with meticulous removal of all
possibly involved soft tissues, including a systematic central lymph node resection, may improve outcomes and
should be included in the routine approach to the suspicious parathyroid lesion. There is no need for a
prophylactic lateral neck dissection.
PubMed-ID: 20640422

Total Parathyroidectomy Without Autotransplantation for Renal Hyperparathyroidism.
Br J Surg, 97(11):1674-9.
Coulston JE, Egan R, Willis E, Morgan JD. 2010.
BACKGROUND: Parathyroidectomy is the standard treatment for renal hyperparathyroidism although
controversy exists about the optimal surgical procedure. Total parathyroidectomy without either
autotransplantation or thymectomy is one suggested approach. This study reviewed the medium- to long-term

ESES Review of Recently Published Literature 2010-3                                                Page 47 of 68
results of this procedure. METHODS: A retrospective review was undertaken of patients undergoing total
parathyroidectomy between August 2000 and March 2009. The procedure was performed by a single surgeon
and median follow-up was 31 (range 1-120) months. RESULTS: Data were obtained on 115 patients with no re-
explorations for bleeding or clinical recurrent laryngeal nerve injuries. The rate of postoperative hypocalcaemia
on the day after surgery was 15.7 per cent. Thirty-three patients (28.7 per cent) had an undetectable parathyroid
hormone level at the end of follow-up. Fourteen patients (12.2 per cent) developed recurrent
hyperparathyroidism with a median parathyroid hormone level of 35.4 (range 5.4-200.0) pmol/l. The reoperation
rate was 3.5 per cent. Thymectomy tissue, taken if all four glands could not be identified, revealed no
parathyroid glands. CONCLUSION: Total parathyroidectomy alone has minimal associated morbidity or
mortality, and a good medium- to long-term clinical outcome with a low recurrence rate.
PubMed-ID: 20641052

Persistent Symptomatic Improvement in the Majority of Patients Undergoing Parathyroidectomy for
Primary Hyperparathyroidism.
Langenbecks Arch Surg, 395(7):941-6.
Gopinath P, Sadler GP, Mihai R. 2010.
BACKGROUND: Parathyroidectomy for primary hyperparathyroidism (PHPT) is followed by a decrease in the
severity of symptoms reported on the Pasieka's parathyroid symptoms score (PPSS) and SF-36 questionnaires.
Some argue that such benefits are short-lived. This study investigates the severity of symptoms at more than 12
months after parathyroidectomy. METHODS: A prospective database collected clinical/operative data on
consecutive patients with PHPT. PPSS was calculated as the sum of the 13 parameters self-assessed using a
visual analog scale. SF-36(v2) was analyzed using commercially available software (QualityMetric Inc., Lincoln,
USA). RESULTS: Over 3-year interval, 166 patients (119 F/47 M, age 15-89 years) were operated for with PHPT
(Ca 2.90 +/- 0.25 mmol/L, PTH 21.64 +/- 23.05 pmol/L). Their preoperative PPSS ranged 0-1,260 (median 413)
and did not correlate with the severity of hypercalcemia. One hundred and seven patients responded when
contacted by post at 18 +/- 6 months postoperatively. Their postoperative PPSS was significantly lower (398 +/-
226 to 231 +/- 203, p < 0.001) and in 55 of 107 patients the severity of symptoms reduced by at least 50%. Most
significant improvements were for mood (36 +/- 33 vs. 16 +/- 23), weakness/tiredness (37 +/- 32 vs. 17 +/- 23),
irritability (35 +/- 31 vs. 17 +/- 21), and thirst (37 +/- 32 vs. 18 +/- 25; p < 0.0001). Physical and mental
component scores of SF-36 questionnaire improved in patients whose PPSS decreased postoperatively.
CONCLUSION: Symptomatic benefits persist for at least 1 year after parathyroidectomy in the majority of
patients with PHPT.
PubMed-ID: 20658300

Long-Term Results of Surgery for Lithium-Associated Hyperparathyroidism.
Br J Surg, 97(11):1680-5.
Jarhult J, Ander S, Asking B, Jansson S, Meehan A, Kristoffersson A, Nordenstrom J. 2010.
BACKGROUND: Lithium therapy for affective bipolar disease is frequently associated with hyperparathyroidism
(HPT), but the results of surgical treatment are virtually unknown. The aim of this retrospective review was to
analyse the long-term outcome after surgery for lithium-induced HPT in a large series of patients. METHODS:
Seventy-one patients on chronic lithium therapy who underwent surgery in three university and three district
hospitals in Sweden were followed for a median of 6.3 years. Histopathology, complications of surgery and
normocalcaemia at 6 months after surgery and last follow-up were analysed. RESULTS: The primary
histopathological diagnoses were adenoma (45 per cent), double adenomas (3 per cent) and hyperplasia (52 per
cent). No permanent paresis of the recurrent laryngeal nerve was recorded but 13 per cent of the patients
suffered from permanent hypoparathyroidism. At follow-up, the rate of persistent and recurrent HPT was 42 per
cent regardless of the histopathological diagnosis. CONCLUSION: The results of conventional surgery for
lithium-associated HPT are poor. The surgical approach should be adjusted for the multiglandular disease that is
usually the cause of HPT in patients on chronic lithium therapy.
PubMed-ID: 20665482

Totally Endoscopic Lateral Parathyroidectomy: Prospective Evaluation of 200 Patients. ESES 2010
Vienna Presentation.
Langenbecks Arch Surg, 395(7):935-40.
Fouquet T, Germain A, Zarnegar R, Klein M, De TN, Claude MJ, Ayav A, Bresler L, Brunaud L. 2010.
PURPOSE: Several new minimally invasive techniques (mini-open, video-assisted, and endoscopic procedures)

ESES Review of Recently Published Literature 2010-3                                               Page 48 of 68
for parathyroidectomy have been described. However, totally endoscopic lateral approach parathyroidectomy
(Henry technique) is not routinely performed. METHODS: This is a prospective study of 200 consecutive patients
that underwent totally endoscopic lateral parathyroidectomy. RESULTS: Two hundred of 387 patients (52%) with
primary hyperparathyroidism were included. Fifty-six patients (28%) were converted to open parathyroidectomy.
Causes for conversion were lack of intraoperative localization (11%), difficult dissection (10%), bleeding (4%),
failure of normalization of IOPTH results (2%), and other causes (1%). Gland localization (areas 1 to 2 versus
area 3) and CaPTHus score (<3 versus >/=3) were not associated with the risk of conversion. Mean
postoperative follow-up was 13 months, and 196 patients (98%) were cured. CONCLUSIONS: Totally
endoscopic lateral approach can be proposed in more than half of the patients with good immediate results.
Conversion rate remains important and may explain low acceptance rate of this technique.
PubMed-ID: 20694475

25-Hydroxy Vitamin D Deficiency Causes Parathyroid Incidentalomas.
Langenbecks Arch Surg, 395(7):919-24.
Kirkby-Bott J, El-Khatib Z, Soudan B, Caiazzo R, Arnalsteen L, Carnaille B. 2010.
PURPOSE: 25-OH D3 (D3) deficiency causes secondary hyperparathyroidism. Asymmetric gland hypertrophy
may also lead to unnecessary parathyroid gland resection by mistaking these glands for parathyroid
incidentalomas. We tested the hypothesis that D3 deficiency causes parathyroid gland hypertrophy. METHOD:
This is a prospective study of 100 consecutive patients undergoing total thyroidectomy. Pre-operative D3
measurement was made at first presentation and on the day after surgery. During thyroidectomy, the parathyroid
glands were searched for and measured. Using an ellipsoid volume calculator, the gland volume was calculated.
This was correlated with D3 and other possible confounding factors. RESULTS: Normal parathyroid volume is
25.1 mm(3). Parathyroid gland size correlated with D3 levels, p < 0.001. There is a greater asymmetry in gland
volume in those patients with the lowest levels of D3 (Spearman's rank correlation coefficient r = -0.51). There
was a significant difference in individual gland volume between D3 levels >30 ng/ml and those <30 ng/ml.
However, there was no difference in mean gland volume between these groups. There was no difference in
correlation according to pathology or thyroid specimen weight. CONCLUSION: There is a significant difference in
both individual gland volume and variation in parathyroid gland volume according to D3 levels. Patients with a
D3 level <30 ng/ml have a more asymmetrical hyperplasia corresponding with parathyroid incidentalomas. D3
levels should be measured pre-operatively in all patients undergoing total thyroidectomy to avoid unnecessary
parathyroid resection.
PubMed-ID: 20717694

[Transoral Partial Parathyroidectomy]
Transorale Partielle Parathyreoidektomie.
Chirurg, 81(11):1020-5.
Karakas E, Steinfeldt T, Gockel A, Sesterhenn A, Bartsch DK. 2010.
Improvements in minimally invasive surgical techniques have resulted in the development of natural orifice
transluminal endoscopic surgery (NOTES) to minimize operative trauma and perioperative morbidity.
Considering the embryologic origin and development of the thyroid and parathyroid glands and their descent
during embryogenesis into the final position in the neck, a transoral access to the thyroid region via a sublingual
mucosal incision seems to be feasible. After implementation and improvement of a transoral access to the
thyroid region in an animal model and human cadavers, we now report the first transoral excision of a
parathyroid adenoma in a 37-year-old woman suffering from primary hyperparathyroidism.
PubMed-ID: 20835695

Intraoperative Parathyroid Hormone Monitoring to Determine Long-Term Success of Total
Parathyroidectomy for Secondary Hyperparathyroidism.
Head Neck, 33(3):293-6.
Moor JW, Roberts S, Atkin SL, England RJ. 2011.
BACKGROUND: Use of intraoperative parathyroid hormone (ioPTH) monitoring during total parathyroidectomy
for secondary hyperparathyroidism is common, although its ability to predict long-term normoparathyroid state is
not known. METHODS: Prospective evaluation of 57 consecutive patients undergoing total parathyroidectomy
for renal hyperparathyroidism with ioPTH monitoring and follow-up PTH assays were used to categorize the
patients into 3 groups: success, adequate biochemical control, and failure. RESULTS: There was no statistically
significant difference in percentage reduction of ioPTH between the 3 groups (p = .07), although there was a

ESES Review of Recently Published Literature 2010-3                                                  Page 49 of 68
moderate negative correlation between percentage reduction of ioPTH and percentage reduction of PTH at
follow-up (R = 0.57). CONCLUSIONS: When used under current guidelines, ioPTH monitoring is of no use in
predicting long-term cure for these patients because it does not predict success. Patients that undergo total
parathyroidectomy are required to have long-term calcium and PTH assay follow-up because
normoparathyroidism cannot be assumed. Using the regression equation calculated, success may be predicted
for future patients. (c) 2010 Wiley Periodicals, Inc. Head Neck, 2010.
PubMed-ID: 20848450

Operative Failures After Parathyroidectomy for Hyperparathyroidism: the Influence of Surgical Volume.
Ann Surg, 252(4):691-5.
Chen H, Wang TS, Yen TW, Doffek K, Krzywda E, Schaefer S, Sippel RS, Wilson SD. 2010.
OBJECTIVE: To determine whether surgical volume influences the cause of operative failures after
parathyroidectomy for hyperparathyroidism. SUMMARY AND BACKGROUND DATA: The surgical success rate
for hyperparathyroidism from high-volume centers exceeds 95%, but some patients have unsuccessful
parathyroidectomies. Although operative failure can be due to hyperfunctioning parathyroid glands in ectopic
locations, less experienced surgeons may be more likely to miss an abnormal parathyroid in normal anatomic
locations, which we describe as "preventable operative failure." METHODS: We used 2 prospective databases
containing over 2000 consecutive patients who underwent parathyroidectomy. We identified 159 patients with
persistent/recurrent hyperparathyroidism subsequently cured with additional surgery. The initially failed
operations were classified as being performed at high- (>50 cases/yr) or low-volume (<50 cases/yr) hospitals.
Hospital volume was obtained from a Wisconsin state database of 89 hospitals, which reported 6336 parathyroid
operations during the same decade. RESULTS: Patients who initially failed their operation performed at the
high- or low-volume centers were similar with regard to age, laboratory values, gender, and parathyroid weights.
Despite a higher incidence of multigland disease (which increases the likelihood of operative failure) in the high-
volume group, patients in the low-volume group were more likely to have a missed parathyroid gland in a normal
anatomic location (89% vs. 13%, P < 0.0001), and thus a higher proportion of preventable operative failures.
CONCLUSIONS: Surgical volume influences the failure pattern after parathyroidectomy for hyperparathyroidism.
Preventable operative failures are more common in low-volume centers.
PubMed-ID: 20881776

Effectiveness of Cinacalcet in Patients With Recurrent/Persistent Secondary Hyperparathyroidism
Following Parathyroidectomy: Results of the ECHO Study.
Nephrol Dial Transplant,
Zitt E, Rix M, Urena TP, Fouque D, Jacobson SH, Petavy F, Dehmel B, Ryba M. 2010.
Background. Progressive secondary hyperparathyroidism (sHPT) is characterized by parathyroid gland
hyperplasia which may ultimately require parathyroidectomy (PTX). Although PTX is generally a successful
treatment for those patients subjected to surgery, a significant proportion develops recurrent sHPT following
PTX. ECHO was a pan-European observational study which evaluated the achievement of KDOQI(TM)
treatment targets with cinacalcet use in patients on dialysis. Previously published results showed that cinacalcet
plus flexible vitamin D therapy lowered serum PTH, phosphorus and calcium in the clinical practice with similar
efficacy as seen in phase III trials. Methods. This subgroup analysis of ECHO describes the real-world cinacalcet
treatment effect in patients with recurrent or persistent sHPT after PTX (n = 153) compared to sHPT patients
without prior history of PTX (n = 1696). Results. Both groups of patients had substantially elevated serum PTH
with comparable sHPT severity at baseline. After 12 months of cinacalcet treatment, 20.3% (26/128) of patients
with prior PTX and 18.2% (253/1388) of patients without prior PTX achieved serum PTH and Ca x P values
within the recommended KDOQI(TM) target ranges. Conclusions. Our data support the successful use of
cinacalcet in patients with recurrent/persistent sHPT after PTX.
PubMed-ID: 20947534

Response to "Tertiary Hyperparathyroidism: Is Less Than a Subtotal Resection Ever Appropriate? A
Study on Long-Term Outcomes".
Surgery, 148(5):1044-5.
Triponez F, Clark OH, Evenepoel P. 2010.
PubMed-ID: 20951866

ESES Review of Recently Published Literature 2010-3                                                 Page 50 of 68
Vitamin D Status, Physical Performance and Body Mass in Patients Surgically Cured for Primary
Hyperparathyroidism Compared With Healthy Controls - a Cross-Sectional Study.
Clin Endocrinol (Oxf), 74(1):130-6.
Amstrup AK, Rejnmark L, Vestergaard P, Sikjaer T, Rolighed L, Heickendorff L, Mosekilde L. 2011.
OBJECTIVE: Low plasma 25-hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body
mass index (BMI) are well-known characteristics of primary hyperparathyroidism (PHPT). Mechanisms for low
25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. Muscle strength is
reported to increase following surgical cure, but whether the improvement corresponds to healthy controls'
performances remains largely unknown. PATIENTS: We studied 51 patients with former PHPT [mean age
61(36-77) years] successfully treated by surgery [mean time since operation 7.4(5-15) years] and 51 sex- and
age-matched controls. MEASUREMENTS: Physical performance include "repeated chair stand" (RCS), "timed
up and go" (TUG), muscle strength [hand grip, elbow flexion/extension and knee flexion/extension (60 degrees
/90 degrees )], postural stability, biochemistry and anthropometric indices. RESULTS: Forty-one cases had
pathologically verified adenoma, three had hyperplasia and three had uncertain diagnosis whereas four had
missing data. Dietary calcium intake, vitamin D supplementation and biochemistry including PTH and 25OHD
levels did not differ between groups. Former patients had significantly higher BMI (28.8 +/- 6.0 kg/m(2)) than
controls (26.0 +/- 4.7kg/m(2)). Muscle pain was more frequently reported by cases than controls, and cases
performed RCS slower than controls (P = 0.02). Furthermore, female cases had lower muscle strength in knee
flexion 60 degrees (P = 0.02) and 90 degrees (P = 0.05). Former patients no longer differed from controls after
adjustment for BMI. CONCLUSION: Following cure, 25OHD levels are normalized suggesting 25OHD
insufficiency is not a constitutional characteristics in patients with PHPT. Increased BMI seems to be sustained.
Whether this is caused by decreased muscle strength or reduced muscular performance causes adiposity needs
further investigations.
PubMed-ID: 21044111

Localization of Metastatic Parathyroid Carcinoma by 18F FDG PET Scanning.
J Clin Endocrinol Metab, 95(11):4844-5.
Gardner CJ, Wieshmann H, Gosney J, Carr HM, Macfarlane IA, Cuthbertson DJ. 2010.
PubMed-ID: 21051579

Reoperative Parathyroidectomy: Location of Missed Glands Based on a Contemporary Nomenclature
Arch Surg, 145(11):1065-8.
Silberfein EJ, Bao R, Lopez A, Grubbs EG, Lee JE, Evans DB, Perrier ND. 2010.
OBJECTIVES: To evaluate and categorize the locations of missed parathyroid glands found during reoperative
parathyroidectomy and to determine any factors associated with these locations. DESIGN: Retrospective cohort
study. SETTING: Tertiary referral center. PATIENTS: Fifty-four patients who underwent reoperative
parathyroidectomy for persistent or recurrent hyperparathyroidism from January 1, 2005, through January 1,
2009. MAIN OUTCOME MEASURES: Location of missed parathyroid glands and their association with
continuous variables were analyzed using a Kruskal-Wallis test, and associations between gland location and
categorical variables were evaluated using the Fisher exact test. RESULTS: Among 54 patients, 50 abnormal
parathyroid glands were identified, resected, and classified as follows: 5 (10%) were type A (adherent to the
posterior thyroid capsule); 11 (22%), type B (behind the thyroid in the tracheoesophageal groove); 7 (14%), type
C (close to the clavicle in the prevertebral space); 3 (6%), type D (directly over the recurrent laryngeal nerve); 9
(18%), type E (easy to identify; near the inferior thyroid pole); 13 (26%), type F (fallen into the thymus); and 2
(4%), type G (gauche, within the thyroid gland). No demographic, biochemical, or pathological factors were
significantly associated with gland location. Among the 43 patients followed up for 6 months, 40 (93%) had
documented cures. CONCLUSIONS: Missed glands after parathyroidectomy for hyperparathyroidism can be
found in standard locations in most cases. A standardized nomenclature system based on the regional anatomy
and the embryology of the parathyroid glands can guide a systematic exploration for parathyroid adenomas that
are not easily identified and facilitate communication about gland locations.
PubMed-ID: 21079094

Durability of Focused Minimally Invasive Parathyroidectomy in Young Patients With Sporadic Primary
Ann Surg Oncol,

ESES Review of Recently Published Literature 2010-3                                                  Page 51 of 68
Oucharek JJ, O'Neill CJ, Suliburk JW, Sywak MS, Delbridge LW, Sidhu SB. 2010.
BACKGROUND: Historically, multigland hyperplasia was believed to be the predominant cause of primary
hyperparathyroidism (PHPT) in young patients, and hence a relative contraindication for minimally invasive
parathyroidectomy. Recent studies, however, demonstrate that the most common aetiology across all age
groups is a solitary functioning adenoma. The aim of this study was to compare long-term outcomes in young
patients (</=45 years), especially those under 30 years of age, with their older counterparts (>45 years) following
focused minimally invasive parathyroidectomy (FMIP). MATERIALS AND METHODS: Patients </=45 years who
underwent FMIP between January 1999 and December 2007 were identified from an endocrine surgery
database and compared with a matched control group of patients >45 years old also undergoing FMIP within
that time period. The patients' most recent calcium levels (>/=6 months postoperatively) were examined to
establish recurrence rates. Recurrence was defined as an elevation of serum calcium more than 6 months after
surgery following initial postsurgical normocalcemia. RESULTS: A total of 117 patients </=45 years and 160
patients >45 years who underwent FMIP were examined. Follow-up calcium levels were available for 72% of
patients. The median length of follow-up was 46 months. No recurrences were identified in both the younger and
older cohort of patients; therefore, no statistically significant difference in rates of recurrence could be
determined between age groups. CONCLUSION: Recurrence of PHPT following FMIP is rare with no evidence
of a higher incidence in younger patients. FMIP can be safely offered to young patients as a long-term durable
treatment option.
PubMed-ID: 21108046

Accuracy of 4-Dimensional Computed Tomography in Poorly Localized Patients With Primary
Surgery, 148(6):1129-37.
Lubitz CC, Hunter GJ, Hamberg LM, Parangi S, Ruan D, Gawande A, Gaz RD, Randolph GW, Moore FD, Jr.,
Hodin RA, Stephen AE. 2010.
BACKGROUND: Four-dimensional computed tomography (4D-CT) utilizes multiplanar images and perfusion
characteristics to identify abnormal parathyroid glands. We assessed the role of 4D-CT in patients with
inconclusive preoperative ultrasound and sestamibi localization studies. METHODS: Adult patients with primary
hyperparathyroidism with negative or discordant standard imaging who underwent both localization with 4D-CT
and operative intervention for curative intent were included. Patient characteristics, 4D-CT scan results
compared with operative findings, and curative proportion were assessed. RESULTS: Of the 60 patients, 4D-CT
accurately lateralized 73% and localized 60% of abnormal glands found at operation. Single candidate lesions
(46/60) were confirmed at operation in 70%. When multiple lesions were identified on 4D-CT (14/60), accuracy
dropped to 29% (P = .03). The accuracy of 4D-CT was not different between primary and reoperative cases (P =
.79). Of the 8 patients with multigland disease diagnosed perioperatively, 5 had multiple candidate lesions noted
on 4D-CT. In 94% (48/51) of patients, a >50% drop in intraoperative parathormone (IOPTH) level was achieved
after resection and 87% (48/55) had long-term cure with a median follow-up of 221 days. CONCLUSION: 4D-CT
identifies the more than half of abnormal parathyroids missed by traditional imaging and should be considered in
cases with negative or discordant sestamibi and ultrasound. Bilateral exploration is warranted when multiple
candidate lesions are reported on 4D-CT. Multigland disease remains a challenging entity.
PubMed-ID: 21134543

The Number of Needle Passes Affects the Accuracy of Parathyroid Hormone Assay With Intraoperative
Parathyroid Aspiration.
Am J Surg, 200(6):701-5.
Guerrero MA, Suh I, Vriens MR, Shen WT, Gosnell J, Kebebew E, Clark OH, Duh QY. 2010.
INTRODUCTION: Intraoperative aspiration of a nodule and parathyroid hormone (PTH) assay has been shown
to accurately confirm parathyroid tissue. However, the reported aspiration technique varies in the literature. We
sought to determine if the number of passes affected the accuracy of PTH analysis. METHODS: A prospective
analysis was performed on 25 consecutive patients who underwent a parathyroidectomy for primary
hyperparathyroidism. The excised parathyroid gland was aspirated using 1, 3, and 5 passes. The data were
analyzed using the Wilcoxon rank, chi-square, and Fisher exact tests to calculate the 2-tailed P value.
RESULTS: Of the 26 glands aspirated, the mean PTH value varied with the number of passes, 2,073 pg/mL for
1 pass, 2,347 for 3 passes, and 2,695 for 5 passes (P = .02). Accuracy was dependent on the number of
passes, with 5 passes (P = .018) having less PTH variation than 1 or 3 passes. CONCLUSIONS: Aspiration of
nodules to determine the PTH level helps confirm the presence of parathyroid tissue. The number of needle
passes affects the accuracy of the PTH level, with 5 passes being the optimal number of passes to attain no

ESES Review of Recently Published Literature 2010-3                                                 Page 52 of 68
false-negative results.
PubMed-ID: 21146006

Parathyroid Surgery in the Elderly.
Oncologist, 15(12):1273-84.
Morris LF, Zelada J, Wu B, Hahn TJ, Yeh MW. 2010.
INTRODUCTION: The prevalence of primary hyperparathyroidism (PHPT) is expected to increase in developed
nations as the aged population grows. This review discusses issues related to PHPT in the elderly population
with a focus on differences in disease presentation, medical and surgical management, and outcomes.
METHODS: Literature review of English-language studies of PHPT or parathyroidectomy (PTx) in the elderly
was performed. Surgical literature reviewed included original clinical studies published after 1990. Priority was
given to studies with >30 patients where institutional practice and outcomes have not changed significantly over
time. RESULTS: Elderly patients primarily present with nonclassic symptoms of PHPT that can sometimes be
missed in favor of other diagnoses. They have equivalent surgical outcomes, including morbidity, mortality, and
cure rates, compared with younger patients, although their length of hospital stay is significantly longer. Several
recent studies demonstrate the safety and efficacy of outpatient, minimally invasive parathyroidectomy in an
elderly population. Patients are referred for PTx less frequently with each advancing decade, although surgical
referral patterns have increased over time in centers that offer minimally invasive parathyroidectomy. Elderly
patients experience increased fracture-free survival after PTx. The majority of elderly patients report
symptomatic relief postoperatively. CONCLUSION: PTx can offer elderly patients with PHPT improved quality of
life. PTx is safe and effective in elderly patients, and advanced age alone should not deter surgical referral.
PubMed-ID: 21159725

Shifting Incidence of Solitary Adenomas in the Era of Minimally Invasive Parathyroidectomy. A Multi-
Institutional Study.
Ann Surg Oncol, 18(4):1041-6.
Twigt BA, Vollebregt AM, van DT, Smits AB, Consten EC, van Vroonhoven TJ, Vriens MR, Borel R, I. 2011.
BACKGROUND: Previously, when a conventional neck exploration (CNE) without preceding diagnostic imaging
was the surgical treatment for patients with primary hyperparathyroidism (pHPT) solitary adenomas were
observed in 69-88% of patients. The advent of minimally invasive parathyroidectomy (MIP), aiming at a
preoperatively identified parathyroid abnormality may be associated with a different incidence of solitary and
multiglandular parathyroid disease. MATERIALS AND METHODS: In a cohort of 467 patients with sporadic
pHPT who preferentially underwent MIP in four hospitals in the same geographical region, the incidence of
solitary adenomas, multiple adenomas, and multiglandular hyperplasia (MGD) was evaluated. RESULTS: A total
of 367 patients were scheduled for MIP; 100 patients underwent a planned CNE. The overall surgical success
rate of the first operation was 93%, and the cumulative success rate, including a second operative procedure,
was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 patients (91%) and more than one
abnormal gland in 35 patients (8%). A parathyroid carcinoma was diagnosed in four of the 426 patients with a
single abnormal gland. Four gland hyperplasia was observed in 1 patient. In hospitals where diagnostic workup
usually consisted of ultrasound (US) and computed tomography (CT) the incidence of solitary adenomas was
88%, compared with 96% in hospitals where MIBI, US, and CT were used preoperatively (P = 0.007).
CONCLUSIONS: A higher frequency of solitary adenomas was observed than historically reported. The extent of
the preoperative workup influences the number of observed solitary adenomas.
PubMed-ID: 21174159

The Superiority of Minimally Invasive Parathyroidectomy Based on 1650 Consecutive Patients With
Primary Hyperparathyroidism.
Ann Surg, 253(3):585-91.
Udelsman R, Lin Z, Donovan P. 2011.
OBJECTIVE: : To compare the results of minimally invasive parathyroidectomy (MIP) and conventional
parathyroid surgery. BACKGROUND: : Primary hyperparathyroidism is a common endocrine disorder often
treated by surgical intervention. Outpatient MIP, employing image-directed focused exploration under cervical
block anesthesia, has replaced traditional surgical approaches for many patients with primary
hyperparathyroidism. This retrospective review of a prospective database compared MIP with conventional
parathyroid surgery. METHODS: : One thousand six hundred fifty consecutive patients underwent surgery for
primary hyperparathyroidism by a single surgeon between 1990 and 2009 at 2 tertiary care academic hospitals.

ESES Review of Recently Published Literature 2010-3                                                 Page 53 of 68
Conventional bilateral cervical exploration under general anesthesia was performed in 613 patients and MIP was
performed in 1037 cases. Cure rates, complication rates, pathologic findings, length of hospital stay, and total
hospital costs were compared. RESULTS: : Minimally invasive parathyroidectomy is associated with
improvements in the cure rate (99.4%) and the complication rate (1.45%) compared to conventional exploration
with a cure rate of 97.1% and a complication rate of 3.10%. In addition, the hospital length of stay and total
hospital charges were also improved compared to conventional surgery. CONCLUSIONS: : Minimally invasive
parathyroidectomy is a superior technique and should be adopted for the majority of patients with sporadic
primary hyperparathyroidism.
PubMed-ID: 21183844

Trends in Parathyroidectomy Rates in US Hemodialysis Patients From 1992 to 2007.
Am J Kidney Dis,
Li S, Chen YW, Peng Y, Foley RN, St Peter WL. 2010.
BACKGROUND:: Parathyroidectomy rates in hemodialysis patients increased from 1992 to 2002, when
medication choices to manage secondary hyperparathyroidism expanded. STUDY DESIGN:: Retrospective
follow-up registry study. SETTING & PARTICIPANTS:: We evaluated annual cohorts of point-prevalent US
hemodialysis patients with Medicare as primary payer for 1992-2007 (n = 1,063,258 for 1992-1999; 757,207 for
2000-2003; 902,119 for 2004-2007). PREDICTOR:: Comorbid conditions, vitamin D use, previous kidney
transplant, and parathyroid hormone testing were assessed in the previous year. Available bone and mineral
disorder treatment patterns were evaluated. OUTCOMES:: We examined incidence rate trends and patient
characteristics through 2007 to estimate the association between parathyroidectomy and patient factors. Follow-
up was from January 1 of each study year to the earliest in the same year of parathyroidectomy, death, or
December 31. MEASUREMENTS:: We used chi(2) analysis to compare patient characteristics in 3 time frames.
Unadjusted and adjusted parathyroidectomy rates were calculated. Cox regression was used to test the
association of parathyroidectomy and covariates. RESULTS:: Adjusted parathyroidectomy rates increased from
1998 (7.0/1,000 patient-years; 1,045 events), peaked in 2002 (12.8/1,000 patient-years; 2,229 events),
decreased through 2005 (5.4/1,000 patient-years; 1,078 events), and increased in 2006 (8.6/1,000 patient-years;
1,743 events) and 2007 (8.8/1,000 patient-years; 1,832 events). Vitamin D use, virtually undetectable in 1991,
subsequently steadily increased; >80% of patients received vitamin D in 2006. LIMITATIONS:: The study was
not designed to provide causal explanations for observed changes; oral medication use trend data were limited
to one large dialysis provider and may not reflect use patterns in all dialysis facilities; because Medicare is not
the primary payer for all US hemodialysis patients, results do not describe the entire US hemodialysis
population; parathyroid hormone values are lacking in the database. CONCLUSIONS:: Adjusted
parathyroidectomy rates varied substantially from 1992 through 2007. Rates were highest in 1994 and 2002 and
lowest in 1998 and 2005, likely influenced by changing medication use patterns and guideline publication.
PubMed-ID: 21186072

The Two Largest Parathyroid Adenomas in the U.S. Literature.
Am Surg, 76(12):1426-8.
Shifflett GD, Serowka KA, Kenney PJ, Recabaren JA. 2010.
PubMed-ID: 21268311

ESES Review of Recently Published Literature 2010-3                                                Page 54 of 68
- None -

Randomized controlled trials
- None -

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Trends in Adrenalectomy: a Recent National Review.
Surg Endosc, 24(10):2518-26.
Murphy MM, Witkowski ER, Ng SC, McDade TP, Hill JS, Larkin AC, Whalen GF, Litwin DE, Tseng JF. 2010.
BACKGROUND: Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the
1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study
aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative
mortality. METHODS: The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed
during 1998-2006. Univariate and multivariate logistic regression were performed, with adjustments for patient
age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume.
Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated.
RESULTS: Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men
made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%)
were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to
5,323 in 2006 (p < 0.0001, trend analysis). The overall in-hospital mortality was 1.1%, with no significant change.
Advanced age (< 45 years as the referent; >/= 65 years: adjusted odds ratio [AOR], 4.10; 95%; confidence
Interval [CI], 1.66-10.10) and patient comorbidities (Charlson score 0 as the referent; Charlson score >/= 2:
AOR, 4.33; 96% CI, 2.34-8.02) were independent predictors of in-hospital mortality. Indication, year, hospital
teaching status, and hospital volume did not independently affect perioperative mortality. Major postoperative in-
hospital complications occurred in 7.2% of the cohort, with a significant increasing trend (1998-2000 [5.9%] vs
2004-2006 [8.1%]; p < 0.0001, trend analysis). Patient comorbidities (Charlson score 0 as the referent; Charlson
score >/= 2: AOR, 4.77; 95% CI, 3.71-6.14), recent year of surgery (1998-2000 as the referent; 2004-2006:
AOR, 1.40; 95% CI, 1.09-1.78), and benign disease (malignant disease as the referent; benign disease: AOR,
1.98; 95% CI, 1.55-2.53) were predictive of major postoperative complications at multivariable analyses,
whereas laparoscopy was protective (no laparoscopy as the referent; laparoscopy: AOR, 0.62; 95% CI, 0.47-
0.82). CONCLUSION: Adrenalectomy is increasingly performed nationwide for both benign and malignant
indications. In this study, whereas perioperative mortality remained low, major postoperative complications
increased significantly.
PubMed-ID: 20336320

Primary Adrenal Hypercortisolism: Minimally Invasive Surgical Treatment or Medical Therapy? A
Retrospective Study With Long-Term Follow-Up Evaluation.
Surg Endosc, 24(10):2542-6.
Guerrieri M, Campagnacci R, Patrizi A, Romiti C, Arnaldi G, Boscaro M. 2010.
BACKGROUND: Because the most suitable management of subclinical Cushing syndrome (SCS, which involves
hypersecretion of cortisol without clinically evident disease) still is undefined, the current study aimed to compare
retrospectively the outcome for a cohort of patients treated by medical therapy or laparoscopic adrenalectomy
(LA). METHODS: Over a 12-year period, 47 patients with SCS have been treated by means of LA (19 patients,
group A) or medical therapy (28 patients, group B). Group A consisted of 15 women and 4 men with a mean age
of 54.8 years. Eight patients had a left adrenal mass, whereas nine had a right adrenal mass, and one patient
had bilateral lesion. Group B was composed of 18 women and 10 men with a mean age of 57.8 years. Of these
patients, 14 had a left adrenal lesion, 12 had a right adrenal lesion, and 1 had bilateral lesion. The patients were
followed up for a mean 4 years (range, 1-11 years) by both an endocrinologist and a surgeon. RESULTS: In
group A, hypertension improved for 66.3% of the patients; body mass index (BMI) decreased for 47.4%; and
hyperlipidemia based on high-density lypoproteins (HDL) cholesterol, total cholesterol ratio, and triglyceridemic
concentration improved for 63.2% of the patients. No changes in bone parameters were seen after surgery in

ESES Review of Recently Published Literature 2010-3                                                  Page 55 of 68
SCS patients with osteoporosis. Some patients in group B, during their long-term medical therapy, experienced
worsening hypertension (14.2%), hyperlipidemia (17.8%), and diabetes mellitus (8%). CONCLUSIONS: This
retrospective study focused on a cohort of patients with SCS. Their medium long-term follow-up evaluation
showed that LA is better than medical therapy for treating this condition, especially by reducing the
cardiovascular risk (hypertension-hyperlipidemia).
PubMed-ID: 20336323

Pheochromocytoma Does Not Increase Risk in Laparoscopic Adrenalectomy.
Surg Endosc, 24(11):2760-4.
Nau P, Demyttenaere S, Muscarella P, Narula V, Hazey JW, Ellison EC, Melvin WS. 2010.
BACKGROUND: Laparoscopic adrenalectomy (LA) has become the standard approach to an adrenal mass.
This technique provides for decreased convalescence, less postoperative pain, and improved cosmesis. The
use of LA for pheochromocytoma (PHE) has been questioned due to concerns of increased morbidity and
negative hemodynamic sequelae. This study aimed to compare the outcomes of LA for PHE with the results of
LA for other adrenal pathologies. METHODS: A retrospective chart review was performed for an 11-year period
from July 1997 to December 2008. Patient demographics, perioperative data, and outcomes were recorded.
Statistical analysis was performed using SPSS 16.0. Statistical significance was defined as a p value less than
0.05. RESULTS: A total of 102 LA procedures were completed for 95 patients. The data for 33 PHE cases were
compared with the data for 69 non-PHE cases (26 adenomas, 14 aldosteronomas, 5 cortisol-secreting tumors, 5
multinodular hyperplasias, and 19 other disorders). Five LA procedures were converted to open surgery. Four of
these conversions involved patients with PHE (p = 0.03). There was no difference in the mean estimated blood
loss (p = 0.2) or operative time (p = 0.1) between the two groups. The frequency of intraoperative hypertension
and hypotension did not differ between the PHE and non-PHE cohorts. The complication rate was 7.5% for the
PHE group and 6.9% for the non-PHE group (p = 0.7). The patients with PHE had a longer postoperative
hospital stay (3.6 vs 2.3 days; p < 0.001) and overall hospital stay (4.9 vs 2.6 days; p < 0.001). Time in the
intensive care unit (1.1 vs 0.1 days; p < 0.001) and time until oral intake (1.5 vs 1.0 days; p = 0.02) also were
increased in the PHE population. There was one death in the PHE group secondary to congestive heart failure.
CONCLUSIONS: Concerns of increased morbidity related to a laparoscopic approach for patients with a
diagnosis of PHE are unfounded. In this series, the only disparity in outcomes between the two groups was an
increased conversion rate with PHE.
PubMed-ID: 20376497

Malignant Adrenal Neoplasm Masquerading As Worrisome Adrenal Hemorrhage.
Ann Surg Oncol, 17(10):2710-3.
avente-Chenhalls LA, Vella A, Farley DR, Thompson GB, Grant CS, Richards ML. 2010.
BACKGROUND: Adrenal hemorrhage (AH) associated with adrenal neoplasm is rare. This study assesses the
clinical and pathological impact of AH in the setting of malignant adrenal neoplasm to establish management
strategies. MATERIALS AND METHODS: Patients admitted over a 25-year period with a diagnosis of AH and
malignant adrenal neoplasm were retrospectively reviewed. RESULTS: Malignant adrenal neoplasms were
reported in 14 of 217 patients (6.4%) presenting with AH. Of these, 4 were women. Mean age was 56 years. The
most common presenting symptom was abdominal pain (n = 6), followed by altered mental status and shock (2)
and hypercortisolism (1). Five patients were asymptomatic. In 10 patients the adrenal tumor was metastatic.
Four patients had adrenocortical carcinoma (ACC). All primary adrenal tumors were unilateral. Risk factors for
AH were identified in 5 patients (anticoagulation, 3; trauma, 1; and recent surgery, 1). Computed tomography (n
= 12) demonstrated adrenal masses ranging in size from 6.8 to 11.0 cm (mean, 9 cm). Nine patients were
managed by surgical resection (adrenalectomy, 4; radical nephrectomy, 2; adrenalectomy/splenectomy, 1;
adrenalectomy/bowel resection, 1; and laparotomy and packing, 1) Actual survival time ranged from 9 days to
7.8 years (median 329 days). CONCLUSION: Most patients with AH in the setting of malignant adrenal
neoplasm had metastatic tumors to the adrenal glands. These patients do not typically present in hemorrhagic
shock, allowing for adequate preoperative evaluation for function and assessment for primary tumors. Long-term
survival of these patients is rare.
PubMed-ID: 20499282

11C-Metomidate Positron Emission Tomography After Dexamethasone Suppression for Detection of
Small Adrenocortical Adenomas in Primary Aldosteronism.
Langenbecks Arch Surg, 395(7):963-7.

ESES Review of Recently Published Literature 2010-3                                               Page 56 of 68
Hennings J, Sundin A, Hagg A, Hellman P. 2010.
PURPOSE: To evaluate whether dexamethasone suppression treatment can improve (11) C-metomidate
positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism
(PA). MATERIALS AND METHODS: Eleven patients with proven PA and two patients with non-hyperfunctioning
adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before
and 3 days after administration of oral dexamethasone suppression treatment. Small "hot-spot" regions of
interest comprising 4 pixels (SUVhs) and 1 pixel (SUVmax) were placed in the tumour area with the highest
radioactivity concentration and their respective standardised uptake values (SUV) were recorded. RESULTS: All
tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher
in PA compared to nonfunctional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p <
0.05), but tumour SUV was not significantly decreased after suppression in either PA or nonfunctional tumours
(p > 0.05). However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p >
0.05). CONCLUSION: MTO-PET is a highly sensitive method for detecting and categorising even small
adrenocortical tumours in PA. In this series, dexamethasone-suppressed MTO-PET was unable to increase the
tumour-to-normal adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal
venous sampling.
PubMed-ID: 20644954

Results of Adrenal Surgery. Data of a Spanish National Survey.
Langenbecks Arch Surg, 395(7):837-43.
Villar JM, Moreno P, Ortega J, Bollo E, Ramirez CP, Munoz N, Martinez C, Dominguez-Adame E, Sancho J, del
Pino JM, Couselo JM, Carrion A, Candel M, Caceres N, Octavio JM, Mateo F, Galan L, Ramia JM, Aguilo J,
Herrera F. 2010.
PURPOSE: Given the availability of laparoscopy and the rising detection of incidentalomas, indications for
adrenalectomy may be changing. The Endocrine Surgery Section of the Spanish Association of Surgeons
designed a survey to assess its indications, techniques, and results in Spanish Surgical Departments.
METHODS: Collected data included hospital and department type, yearly hospital volume of procedures;
location studies and preoperative preparation performed, indications, surgical approach and instruments used,
and results in terms of morbidity and overall hospital stay. The analysis included a comparison between results
of high- or low-volume centers and surgeons, using the Student's t test for quantitative and chi-square test for
qualitative variables. Level of significance was set at 0.05. RESULTS: Nineteen centers returned the
questionnaire, including 155 adrenalectomies performed in 2008. Most frequent indications were
pheochromocytoma (23.2%), aldosteronoma (16.7%), incidentaloma (12.2%), metastasis (10.3%), Cushing
adenoma (9.6%), and carcinoma (3.8%). Laparoscopy was performed in 83.9% of cases (9.4% required
conversion to laparotomy). Four patients required urgent reoperation. Average hospital stay: 4.6 days (3.3 days
after laparoscopy, 7 days after laparotomy). High-volume centers had a greater proportion of laparoscopically
treated cases (p = 0.008), more malignant lesions treated (p = 0.03), a shorter overall stay (p < 0.0001), and a
shorter stay after laparotomic adrenalectomy (p = 0.01). High-volume surgeons had similar results, and less in-
hospital morbidity (p = 0.02). CONCLUSIONS: In Spain, adrenalectomy is performed in hospitals of varying
complexity. Laparoscopic approach is the rule, with good results in terms of morbidity and stay. High-volume
centers and surgeons had best results in terms of use of minimally invasive surgery and hospital stay.
PubMed-ID: 20658299

Improved Survival in Patients With Stage II Adrenocortical Carcinoma Followed Up Prospectively by
Specialized Centers.
J Clin Endocrinol Metab, 95(11):4925-32.
Fassnacht M, Johanssen S, Fenske W, Weismann D, Agha A, Beuschlein F, Fuhrer D, Jurowich C, Quinkler M,
Petersenn S, Spahn M, Hahner S, Allolio B. 2010.
CONTEXT: Median survival in stage II adrenocortical carcinoma (ACC) differs widely in published series ranging
between 23 and more than 60 months. We hypothesized that these results may have been affected by a referral
bias because many patients may contact specialized centers only after recurrence. OBJECTIVE: The objective
of the study was a comparison of outcome in patients with stage II ACC who were followed up prospectively
early after surgery and were counseled by a specialized center (prospective group) with patients who registered
with the German ACC registry later than 4 months after diagnosis (retrospective group). PATIENTS/METHODS:
The study was a cohort analysis in 149 adult patients with stage II ACC. RESULTS: Patients who were followed
up prospectively (n = 30) had a lower recurrence rate and a superior 5-yr survival compared with the 119
patients in the retrospective group (30 vs. 74%, P < 0.01 and 96 vs. 55%, P < 0.05, respectively). In the

ESES Review of Recently Published Literature 2010-3                                                 Page 57 of 68
retrospective group, 67% of the patients had registered only after disease recurrence. In the remaining patients,
the recurrence rate was low (21%), and the 5-yr survival was greater than 95%. More patients in the prospective
group received adjuvant mitotane (53 vs. 16%, P < 0.001), and adjuvant mitotane was associated with improved
survival [hazard risk 0.35 (95% confidence interval 0.13-0.97); P = 0.04]. However, the survival advantage was
maintained when only patients without mitotane therapy were analyzed. CONCLUSIONS: Patients who are
followed up prospectively after surgery for stage II ACC and receive early specialized care have a much better
prognosis than previously reported due to a major referral bias in previous series and use of adjuvant mitotane.
These findings will impact on the perception of prognosis in newly diagnosed stage II ACC.
PubMed-ID: 20668036

Proposal for Modification of the ENSAT Staging System for Adrenocortical Carcinoma Using Tumor
Langenbecks Arch Surg, 395(7):955-61.
Miller BS, Gauger PG, Hammer GD, Giordano TJ, Doherty GM. 2010.
PURPOSE: Various staging systems for adrenocortical carcinoma (ACC) have been proposed. We hypothesized
that incorporating tumor grade into the current European Network for the Study of Adrenal Tumors (ENSAT)
staging system would improve the ability to more accurately predict time to recurrence and death. METHODS: A
retrospective review of patients included in the University of Michigan ACC database from 2005 to 2009 was
done; and stage, tumor grade, time to recurrence, and death were recorded and analyzed using the Cox
regression and Kaplan-Meier survival curves. RESULTS: Ninety one patients had complete information for
inclusion. The median follow-up was 24 months while the median time to recurrence was 4.1 months. There
were 28 deaths; overall, tumor grade showed a significant difference in time to tumor recurrence (p = 0.011) and
time to death (p = 0.004). Time to death among stage 2 patients separated into those with high- and low-grade
tumors reached statistical significance (p = 0.05), and notable but not statistically significant differences were
identified in all stages. Based on tumor grade and survival curves, modifications to the current ENSAT staging
system were made. CONCLUSION: Tumor grade plays a significant role in the outcome of patients with ACC.
High-grade tumors are associated with shorter disease-free intervals and shorter overall survival. The proposed
modification of the ENSAT staging system allows for incorporation of tumor grade when predicting overall
PubMed-ID: 20694732

Size of the Tumor and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS): Can They Predict
World J Surg, 34(12):3022-8.
Agarwal A, Mehrotra PK, Jain M, Gupta SK, Mishra A, Chand G, Agarwal G, Verma AK, Mishra SK, Singh U.
BACKGROUND: Size can predict malignancy in adrenocortical tumors, but the same extrapolation for
pheochromocytomas (PCC) is controversial. The goal of this study was to find a correlation between the tumor
size and malignant potential of PCC and determine whether the "Pheochromocytoma of the adrenal gland
scaled score" (PASS) proposed by Thompson can be applied to predict malignancy. METHODS: A retrospective
analysis of patients with PCC operated on from 1991 to 2007 revealed 98 PCC removed from 93 patients.
Tumor size was available for 90 tumors. Six (6.4%) patients had proven malignancy. Five familial cases were
excluded from the PASS analysis. RESULTS: Of the benign cases, none developed recurrence or metastasis.
There were 54 (60%) tumors > 6 cm and 36 (40%) tumors </= 6 cm. All 12 PASS parameters were individually
present in higher frequency in the >6-cm group; but the difference was not statistically significant except cellular
monotony (p = 0.02). Overall, a PASS </= 4 was found in 57 patients. Mean PASS was statistically significantly
higher in the >6-cm group (4.4 vs. 3.3, p = 0.04). Of the sporadic benign cases, 21 (41%) patients with tumor
size > 6 cm had a PASS of >4, and none of them developed metastasis. PASS </= 4 was found in 25 (81%)
PCC in the </=6-cm group, and none developed metastases. PASS >/= 4 was found in six (19%) patients in the
</=6-cm group, and none developed metastases. 68 patients completed 5-year follow-up, and the remaining had
a mean follow-up of 28.7 months. No correlation was found between tumor size and PASS > 4 and PASS </= 4
(7.8 cm vs. 7.1 cm; p = 0.23). CONCLUSIONS: Presently there is not enough evidence to indict a large (>6 cm)
PCC as malignant. Furthermore, PASS cannot be reliably applied to PCC for predicting malignancy.
PubMed-ID: 20703467

ESES Review of Recently Published Literature 2010-3                                                 Page 58 of 68
Adrenal Incidentalomas: Risk of Adrenocortical Carcinoma and Clinical Outcomes.
J Surg Oncol, 102(5):450-3.
O'Neill CJ, Spence A, Logan B, Suliburk JW, Soon PS, Learoyd DL, Sidhu SB, Sywak MS. 2010.
INTRODUCTION: The number of incidentally discovered adrenal lesions is increasing due to the widespread
use of abdominal imaging. Although most incidentalomas are benign, larger suspicious lesions will require
adrenalectomy. The aim of this study is to determine the risk of malignancy in patients undergoing surgery for
adrenal incidentaloma; and to compare clinical outcomes in those with adrenocortical carcinoma (ACC) based
on the mode of presentation. METHODS: A retrospective study of consecutive patients who underwent
adrenalectomy between 1995 and 2008 was performed. Data were retrieved from a prospectively maintained
adrenal tumor database. Those with adrenal incidentaloma were selected and histopathology reviewed. All
patients with ACC (presenting with symptoms or incidentally) during the same time period were identified and
clinical outcomes compared. RESULTS: Adrenalectomy was performed in 274 patients of whom 73 (27%) were
characterized pre-operatively as incidentaloma. Benign, non-functioning adrenocortical adenoma was the most
common histopathological finding (46 patients, 63%). There was a trend (P = 0.08) towards increased survival
amongst the seven patients with ACC presenting incidentally compared to the nine patients with symptomatic
ACC. CONCLUSIONS: Adrenal incidentalomas have a small but important risk of malignancy. ACC presenting
as incidentaloma appear to have a more favorable prognosis than symptomatic or functioning ACC.
PubMed-ID: 20734420

Approach to the Patient With an Adrenal Incidentaloma.
J Clin Endocrinol Metab, 95(9):4106-13.
Nieman LK. 2010.
Unsuspected adrenal masses, or incidentalomas, are increasingly found with the widespread use of thoracic and
abdominal imaging. These masses may be hormonally active or nonfunctional and malignant or benign.
Clinicians must determine the nature of the mass to decide what treatment, if any, is needed. Measurement of
precontrast Hounsfield units (HU) and contrast washout on computed tomography scan provide useful
diagnostic information. All patients should undergo biochemical testing for pheochromocytoma, either with
plasma or urinary catecholamine measurements. This is particularly important before surgical resection, which is
routinely recommended for masses larger than 4 cm in diameter without a clear-cut diagnosis and for others with
hormonal secretion or ominous imaging characteristics. Hypertensive patients should undergo biochemical
testing for hyperaldosteronism. Patients with features consistent with Cushing's syndrome, such as glucose
intolerance, weight gain, and unexplained osteopenia, should be evaluated for cortisol excess. Here, the
dexamethasone suppression test and late-night salivary cortisol may be preferred over measurement of urine
cortisol. The ability of surgical resection to reverse features of mild hypercortisolism is not well established. For
masses that appear to be benign (<10 HU; washout, >50%), small (<3 cm), and completely nonfunctioning,
imaging and biochemical reevaluation (pheochromocytoma and hypercortisolism only) at 1-2 yr (or more) is
appropriate. For more indeterminate lesions, repeat evaluation for growth after 3-12 months is useful, with
subsequent testing intervals based on the rate of growth.
PubMed-ID: 20823463

The Changing Face of Pheochromocytoma: Varied Presentations, Better Outcomes.
Arch Surg, 145(9):897-8.
Yeh MW. 2010.
PubMed-ID: 20873011

Approach to the Patient With Adrenocortical Carcinoma.
J Clin Endocrinol Metab, 95(11):4812-22.
Lacroix A. 2010.
Adrenocortical cancer (ACC) is a rare and often aggressive malignancy that requires multidisciplinary expertise
for optimal management. It can present with symptoms of rapidly appearing excess steroid secretion or an
abdominal mass, or it can be discovered incidentally. Thorough imaging and endocrine evaluations can identify
the majority of ACCs amongst adrenal tumors; however, some smaller ACCs are better identified using
fluorodeoxyglucose-positron emission tomography/computed tomography scan. Complete resection by an expert
surgeon is the only potentially curative treatment for ACC, and tumor spillage should be avoided. Histopathology
is important for diagnosis, but immunohistochemistry markers and gene profiling of the resected tumor may
become superior to current staging systems to stratify prognosis. Despite complete resection in stage I-III
tumors, approximately 40% of patients develop metastasis within 2 yr. Some retrospective studies indicate that

ESES Review of Recently Published Literature 2010-3                                                  Page 59 of 68
adjuvant mitotane therapy prolongs disease-free survival, leading several centers to recommend its
administration; prospective studies are under way to provide future evidence-based recommendations. For
locally invading ACC, extensive en bloc resection is attempted, followed by adjuvant mitotane and, in selected
cases, adjuvant radiotherapy. When ACC is not surgically resectable, mitotane therapy is adjusted to reach
serum levels of 14-20 mug/ml. Careful replacement of glucocorticoid and mineralocorticoid deficiency after
surgery or mitotane therapy is important; steroid excess from remaining tumor burden should also be controlled
to avoid its morbidities. For metastatic disease, combination chemotherapy should be administered, if possible,
in the context of multicenter collaborative research protocols. New insights in the molecular pathogenesis of
ACC should allow the development of improved targeted therapies.
PubMed-ID: 21051577

Radiofrequency Ablation for Benign Aldosterone-Producing Adenoma: a Scarless Technique to an Old
Ann Surg, 252(6):1058-64.
Liu SY, Ng EK, Lee PS, Wong SK, Chiu PW, Mui WL, So WY, Chow FC. 2010.
OBJECTIVE: To evaluate the safety and efficacy of radiofrequency ablation (RFA) in treating primary
aldosteronism (PA) due to aldosterone-producing adenoma (APA). BACKGROUND: Radiofrequency ablation is
an established technique for treating malignant solid organ neoplasm. Its application on benign functional
adrenal adenoma has never been prospectively described. METHODS: We prospectively evaluated a patient
cohort with computed tomography (CT)-guided percutaneous RFA performed on functional APA of size 4 cm or
less. Treatment success was defined as complete tumor ablation on follow-up CT scan plus normalization of
serum aldosterone-to-renin ratio (ARR) at 3 to 6 months after RFA. Salvage laparoscopic adrenalectomy was
offered to patients who had failed RFA and remained hypertensive. RESULTS: Between August 2004 and
August 2008, 28 patients were referred for the procedure. Radiofrequency ablation was not performed on 4 APA
because of their close proximity to major vascular structures. Twenty-four patients (11 men and 13 women) with
a median age of 51.5 (range = 34-63) years underwent RFA for 11 right and 13 left APA. The median tumor
diameter was 16.0 (range = 4.0-25.0) mm. There was no periprocedure hypertensive crisis or major morbidity or
mortality. Minor complications occurred in 4 patients (16.7%), including 1 small pneumothorax and 3
retroperitoneal hematomas (< 3 cm), which all resolved on conservative treatment. At 3 to 6 months of follow-up,
CT scan showed complete tumor ablation in all patients (100%). Primary aldosteronism was biochemically
resolved in 23 patients (95.8%). Salvage adrenalectomy was not performed in the single failed patient, as she
remained normotensive on repeated follow-up. The overall success rate of RFA was 95.8%. CONCLUSIONS:
Computed tomography-guided percutaneous RFA is a safe and efficacious alternative to laparoscopic
adrenalectomy in treating patients with PA due to small APA.
PubMed-ID: 21107117

ESES Review of Recently Published Literature 2010-3                                              Page 60 of 68
- None -

Randomized controlled trials
- None -

Other Articles
Endocrine Carcinoma of the Major Papilla: Report of Two Cases and Review of the Literature.
Surg Oncol, 19(4):235-42.
De Palma GD, Masone S, Siciliano S, Maione F, Falleti J, Mansueto G, De RG, Persico G. 2010.
To date, about 100 cases of ampullary NET are reported in International literature. These tumors can cause
symptoms mainly secondary to their periampullary location. Up to 25% of patients have von Recklinghausen's
disease. Carcinoid syndrome is uncommon, unless hepatic metastasis is present. Determination of
histopathology is of utmost importance and involves specific immunohistochemical staining. The published data
indicate that these tumors, metastasize in approximately half of cases irrespective of primary tumor size.
Therefore, radical excision in the form of pancreaticoduodenectomy is recommended regardless of tumor size.
Local excision should be confined to patients unable to tolerate more extensive surgery. We here report two
case of ampullary neuroendocrine tumors presenting as melena and painless jaundice respectively in a 51-year
old man and in a 54-year old man and review the relevant literature, giving special attention to the morphologic
features, clinical characteristics, and treatment modalities associated with this disease process.
PubMed-ID: 19586767

The Significance of Occult Carcinoids in the Era of Laparoscopic Appendectomies.
Surg Endosc, 24(9):2197-9.
Shapiro R, Eldar S, Sadot E, Venturero M, Papa MZ, Zippel DB. 2010.
BACKGROUND: We present data acquired in our institution about the incidence of incidental appendiceal
carcinoids over a period of 16 years. The possibility of occult carcinoids raises the question of appendectomy of
a noninflamed appendix during diagnostic laparoscopy for suspected appendicitis. METHODS: We performed a
retrospective chart analysis of the surgical registry of a university-affiliated tertiary care center of a major
population area for the past 16 years. Data were collected on all patients (n = 7592) who underwent
appendectomy for the presumed diagnosis of acute appendicitis. Outcome measures were the incidence of
incidental carcinoids of the appendix found during appendectomies and whether the introduction of laparoscopic
appendectomy should alter the surgical management of a normal-appearing appendix. RESULTS: A total of 20
carcinoid appendices were resected by open surgery and 17 by laparoscopy. The diagnosis of a carcinoid tumor
was not suspected in any patient before the operation, nor was a tumor identified at the time of the operation. In
6 (16%) patients the appendix appeared normal at the time of the operation. CONCLUSIONS: It has long been
the standard of care to remove any appendix found in laparotomy for suspected appendicitis, but it is not clear
what should be done during laparoscopy for suspected appendicitis when the appendix appears normal. Our
data confirm the presence of occult carcinoids in normal-appearing appendices. Further studies are needed to
determine the clinical significance of this finding.
PubMed-ID: 20174936

Chromogranin A--Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease.
Ann Surg Oncol, 17(9):2427-43.
Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV, Kidd M. 2010.
BACKGROUND: Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they
synthesize, store, and secrete peptides, e.g., chromogranin A (CgA) and amines. A critical issue is late diagnosis
due to failure to identify symptoms or to establish the biochemical diagnosis. We review here the utility of CgA
measurement in NETs and describe its biological role and the clinical value of its measurement. METHODS:
Literature review and analysis of the utility of plasma/serum CgA measurements in NETs and other diseases.
RESULTS: CgA is a member of the chromogranin family; its transcription and peptide processing are well

ESES Review of Recently Published Literature 2010-3                                                Page 61 of 68
characterized, but its precise function remains unknown. Levels are detectable in the circulation but vary
substantially (approximately 25%) depending on which assay is used. Serum and plasma measurements are
concordant. CgA is elevated in approximately 90% of gut NETs and correlates with tumor burden and
recurrence. Highest values are noted in ileal NETs and gastrointestinal NETs associated with multiple endocrine
neoplasia type 1. Both functioning and nonfunctioning pancreatic NETs have elevated values. CgA is more
frequently elevated in well-differentiated tumors compared to poorly differentiated NETs. Effective treatment is
often associated with decrease in CgA levels. Proton pump inhibitors falsely increase CgA, but levels normalize
with therapy cessation. CONCLUSIONS: CgA is currently the best available biomarker for the diagnosis of
NETs. It is critical to establish diagnosis and has some utility in predicting disease recurrence, outcome, and
efficacy of therapy. Measurement of plasma CgA is mandatory for the effective diagnosis and management of
NET disease.
PubMed-ID: 20217257

Pancreatic Cystic Endocrine Tumors: a Different Morphological Entity Associated With a Less
Aggressive Behavior.
Neuroendocrinology, 92(4):246-51.
Boninsegna L, Partelli S, D'Innocenzio MM, Capelli P, Scarpa A, Bassi C, Pederzoli P, Falconi M. 2010.
BACKGROUND: Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their biological features have
been scarcely investigated. Aim: To compare clinical and pathological features of resected non-functioning
sporadic CPETs (NF-CPETs) with solid pancreatic endocrine tumors (SPETs) in a single-institution experience.
METHODS: All patients with a pathologically confirmed diagnosis of sporadic non-functioning pancreatic
endocrine tumors who underwent curative resection between 1990 and 2008 were included. A comparison of
demographic, clinical and pathological characteristics between CPETs and SPETs was made. Univariate and
multivariable analyses were performed to identify preoperative predictors of carcinoma (non-functioning
pancreatic endocrine carcinoma). RESULTS: Twenty-one (11.5%) patients with a histological diagnosis of NF-
CPET were identified. The median age was 60 years (IQR 46.5-73.5 years) and a diagnosis of carcinoma (non-
functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the comparison with NF-SPETs,
no differences were found in terms of gender (p = 0.75), age (p = 0.81), presenting symptoms (p = 0.43),
localization of the tumors (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning pancreatic
endocrine carcinoma was significantly lower in the NF-CPET versus the NF-SPET group (14.3 vs. 40.4%, p =
0.04). By univariate analysis, preoperative predictors of non-functioning pancreatic endocrine carcinoma
included the presence of symptoms (OR 3.96, 95% CI 2.06-7.63) and an increase in the absolute value of
radiological diameter (OR 1.05, 95% CI 1.03-1.07). A cystic morphology of the lesion turned out to be a negative
predictor of carcinoma (OR 0.25, 95% CI 0.70-0.87). These results were confirmed by multivariable analysis.
CONCLUSIONS: NF-CPETs have a measurable propensity to be benign. In those patients affected by small and
asymptomatic NF-CPET a more conservative surgical approach or a follow-up policy could be considered.
PubMed-ID: 20689265

A Nomogram to Assess Small-Intestinal Neuroendocrine Tumor ('Carcinoid') Survival.
Neuroendocrinology, 92(3):143-57.
Modlin IM, Gustafsson BI, Pavel M, Svejda B, Lawrence B, Kidd M. 2010.
Neuroendocrine tumors (NETs) are a heterogeneous group of cancers of which the commonest site is the small
intestine (SI). Most information available to determine tumor behavior reflects univariate assessment of factors or
is anecdotal or experience based. There currently exists no objective multivariate analysis of indices that defines
SI NET prognosis. A key unmet need is the lack of a rigorous mathematical-based tool - a nomogram - for the
assessment of parameters that define progress, determine prognosis and can guide therapy. Since prediction of
NET behavior is a critical criterion in determining clinical strategy, we constructed a NET nomogram (Modlin
Score) for prognosis prediction, patient group comparisons and a guide for stratification of treatment and
surveillance. We used hazard ratio (HR), Cox analysis and Kaplan-Meier analysis of published data and the
current Surveillance, Epidemiology and End Results (SEER) database (approx. 20,000 patients) to develop a
nomogram from 15 variables demonstrated to provide significant multivariate HRs. These included age, gender,
ethnicity, symptoms, urinary 5-hydroxyindoleacetic acid, plasma chromogranin A, liver function tests, tumor size,
invasion, metastasis, histology, Ki-67 index, carcinoid heart disease and therapy (surgery or long-acting
somatostatin analogs). Internal validation was assessed using 33 SI NET patients. A NET nomoscore (Modlin
Score) was developed by HR weighting and stratification into low (<75), medium (75-95) and high risk (>95).
This identified significant differences (p <0.03, Kaplan-Meier) in survival (15.5 +/- 4.3, 9.7 +/- 2.5 and 6.4 +/- 1.1
years, respectively). The Modlin Score was significantly elevated (p <0.01) in deceased compared to alive

ESES Review of Recently Published Literature 2010-3                                                   Page 62 of 68
patients. This nomogram represents an optimized construct based upon currently analyzable data, and
application will facilitate accurate stratification for comparison in clinical trials. External validation and
amplification by identification of additional indices, e.g. molecular biomarkers, are necessary. The development
of a mathematically validated nomogram provides a platform for objective assessment of SI NET disease, a finite
basis for precise prognostication and a tool to guide management strategy.
PubMed-ID: 20733279

Clinical, Histopathologic, and Radiographic Indicators of Malignancy in Head and Neck Paragangliomas.
Otolaryngol Head Neck Surg, 143(4):531-7.
Chapman DB, Lippert D, Geer CP, Edwards HD, Russell GB, Rees CJ, Browne JD. 2010.
OBJECTIVE: The goal of this study is to review our series of head and neck paragangliomas to identify factors
that may help in predicting malignancy. STUDY DESIGN: Case series with chart review. SETTING: Academic
medical center. SUBJECTS AND METHODS: Subjects with head and neck paragangliomas at our institution
from 1976 to current were reviewed. In addition to statistical comparisons of epidemiologic factors, pathologic
and radiographic characteristics were reviewed. RESULTS: Of the 84 subjects, there were seven malignant
paragangliomas (8%). Age was found to be significantly different between the benign and malignant subgroups,
with an average age of 54 +/- 16 and 40 +/- 12 years, respectively (P = 0.02). Pain was a presenting complaint in
five patients with benign disease (6%), and five of the seven malignant patients (71%) presented with pain,
showing a significant association between pain and disease type (P < 0.0001). The odds ratio for a patient with
pain having a malignant tumor was 36 (95% CI: 5.5-234). Enlarging neck mass was noted in all cases of
malignant disease, but only in 31 percent of cases of benign disease (P < 0.0001). In a secondary analysis of
carotid body tumors alone, enlarging neck mass was not found to be significant between benign and malignant
disease (P = 0.14). However, pain continued to be significantly different, with 67 percent of malignant lesions
demonstrating pain, compared with only 11 percent of benign lesions (P = 0.01). CONCLUSION: This study
suggests that pain, a rapidly enlarging neck mass, and younger age are predictive factors of underlying
malignancy, which should prompt one to consider an aggressive diagnostic and management approach.
PubMed-ID: 20869564

Primary Hyperparathyroidism in Patients With Gastric Carcinoid Tumors Type 1: an Unusual
Neuroendocrinology, 92(4):252-8.
Thomas D, Alexandraki K, Nikolaou A, Antoniou S, Kanakis G, Zilos A, Sougioultzis S, Kaltsas G. 2010.
OBJECTIVE: Although a number of familiar syndromes are associated with primary hyperparathyroidism (PHP),
there is no information regarding the prevalence of PHP in other sporadic neuroendocrine diseases. The aim of
this study is to investigate the prevalence of PHP in our group of patients with gastric carcinoid (GC) type 1
tumors. METHODS: Twenty-six patients with biopsy-proven GC type 1 tumors were retrospectively studied. The
diagnosis of PHP was suspected following elevated or high-normal serum calcium levels and elevated or
inappropriate normal parathyroid hormone levels. Further tests for the localization of the hyperfunctioning
parathyroid glands included neck ultrasound, (99m)Tc-SESTAMIBI scanning, and cervical or upper mediastinal
MR imaging studies. Four control groups were also studied: two age- and sex-matched groups of individuals with
(n = 49) and without (n = 34) thyroid autoimmunity and normal endoscopy of the stomach, a third group with
nongastric neuroendocrine tumors (n = 68), and a fourth group with atrophic gastritis and hypergastrinemia,
without gastric endocrine tumors (n = 30). RESULTS: PHP was diagnosed in 4 (15.38%) patients with GC type 1
tumors compared to none of the 4 control groups. Three of the 4 patients with PHP were operated and proved to
have a parathyroid adenoma. No statistically significant differences were observed between patients with or
without PHP in mean gastrin and chromogranin A levels, number of lesions, ki-67 labeling index expression, and
maximum GC type 1 tumor diameter. CONCLUSION: PHP seems to be relatively common, approximately 15%
in the present cohort, in patients with GC type 1 tumors. PHP should be actively looked for in such patients and
treated accordingly.
PubMed-ID: 20924166

ESES Review of Recently Published Literature 2010-3                                               Page 63 of 68
GI and General
- None -

Randomized controlled trials
- None -

Other Articles
Systematic Comparison of Sporadic and Syndromic Pancreatic Islet Cell Tumors.
Endocr Relat Cancer, 17(4):875-83.
Erlic Z, Ploeckinger U, Cascon A, Hoffmann MM, von DL, Winter A, Kammel G, Bacher J, Sullivan M, Isermann
B, Fischer L, Raffel A, Knoefel WT, Schott M, Baumann T, Schaefer O, Keck T, Baum RP, Milos I, Muresan M,
Peczkowska M, Januszewicz A, Cupisti K, Tonjes A, Fasshauer M, Langrehr J, von WP, Agaimy A, Schlimok G,
Lamberts R, Wiech T, Schmid KW, Weber A, Nunez M, Robledo M, Eng C, Neumann HP. 2010.
Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine
neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for
timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our
registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors
(NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically
confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen.
All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large
deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in
VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those
with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly
sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically
significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower
malignancy rate (P<0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in <0.5% of NETs,
while NETs occur in approximately 10% of VHL, virtually exclusively as ICTs, which are rarely the first
presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have
multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.
PubMed-ID: 20660572

Gastroenteropancreatic Neuroendocrine Tumours: the Current Incidence and Staging Based on the
WHO and European Neuroendocrine Tumour Society Classification: an Analysis Based on Prospectively
Collected Parameters.
Endocr Relat Cancer, 17(4):909-18.
Niederle MB, Hackl M, Kaserer K, Niederle B. 2010.
As incidence data on gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have so far only been
retrospectively obtained and based on inhomogeneous material, we conducted a prospective study in Austria
collecting all newly diagnosed GEP-NETs during 1 year. Using the current WHO classification, the tumor, nodes,
metastases (TNM) staging and Ki67 grading and the standard diagnostic procedure proposed by the European
Neuroendocrine Tumor Society (ENETS), GEP-NETs from 285 patients (male: 148; female: 137) were recorded.
The annual incidence rates were 2.51 per 100,000 inhabitants for men, 2.36 per 100,000 for women. The
stomach (23%) was the main site, followed by appendix (21%), small intestine (15%) and rectum (14%). Patients
with appendiceal tumours were significantly younger than patients with tumours in any other site. About 46.0%
were classified as benign, 15.4% as uncertain, 31.9% as well differentiated malignant and 6.7% as poorly
differentiated malignant. Patients with benign or uncertain tumours were significantly younger than patients with
malignant tumours. Among the malignant tumours of the digestive tract, 1.49% arose from neuroendocrine cells.
For malignant gastrointestinal NETs, the incidence was 0.80 per 100,000: 40.9% were ENETS stage I, 23.8%
stage II, 11.6% stage III and 23.8% stage IV. The majority (59.7%) were grade 1, 31.2% grade 2 and 9.1%
grade 3. NETs of the digestive tract are more common than previously reported; the majority show benign
behaviour, are located in the stomach and are well differentiated. G3 tumours are very rare.

ESES Review of Recently Published Literature 2010-3                                               Page 64 of 68
PubMed-ID: 20702725

Role of Imaging in the Preoperative Staging of Small Bowel Neuroendocrine Tumors.
J Am Coll Surg, 211(5):620-7.
Chambers AJ, Pasieka JL, Dixon E, Rorstad O. 2010.
BACKGROUND: Imaging studies are important in the preoperative staging of patients with small bowel
neuroendocrine tumors (NET) and when selecting patients for cytoreduction procedures for metastatic disease.
The purpose of this study was to assess the accuracy of preoperative imaging compared with operative findings
in the staging of small bowel NET. STUDY DESIGN: Sixty-four patients with small bowel NET undergoing
laparotomy and who had preoperative imaging with combinations of CT, MR, and radionuclide scintigraphy were
reviewed. Results of imaging studies were compared with operative findings to assess the ability of these
investigations to detect mesenteric, peritoneal, and hepatic metastases. RESULTS: Mesenteric nodal
metastases were seen on imaging in 47 (73%) patients and were present at laparotomy in 56 (88%) patients.
Peritoneal metastases were seen on preoperative imaging in 4 (6%) patients and found at laparotomy in 16
(25%) patients. Hepatic metastases were seen on imaging in 42 patients (66%) and found at laparotomy in 49
(77%). Sensitivity and specificity for detection of hepatic metastases were 77% and 100% for CT, 82% and
100% for MR, 63% and 100% for (123)I-meta-iodobenzylguanadine scintigraphy, and 63% and 100% for
(111)In-octreotide. Imaging studies failed to detect hepatic metastases in 7 patients and underestimated the
extent of hepatic metastatic disease in 17 patients. CONCLUSIONS: Imaging of small bowel NET, even with
combinations of CT, MR, and radionuclide studies, underestimates the extent of peritoneal, mesenteric, and
hepatic metastatic disease. Accurate staging of small bowel NET might be best performed at the time of
PubMed-ID: 21035044

Carcinoid Tumors of the Rectum: a Multi-Institutional International Collaboration.
Ann Surg, 252(5):750-5.
Shields CJ, Tiret E, Winter DC. 2010.
OBJECTIVE: This study aims to describe recent experience with rectal carcinoids in European and North
American centers. BACKGROUND: While considered indolent, the propensity of carcinoids to metastasize can
be significant. METHODS: Rectal carcinoid patients were identified from prospective databases maintained at 9
institutions between 1999 and 2008. Demographic, clinical, and histologic data were collated. Median follow-up
was 5 years (range, 0.5-10 years). RESULTS: Two hundred two patients were identified. The median age was
55 years (range, 31-81 years). The majority of tumors were an incidental finding (n = 115, 56.9%). The median
tumor size was 10 mm (range, 2-120 mm). Overall, 93 (49%) tumors were limited to the mucosa or submucosa,
45 (24%) involved the muscularis propria, 29 (15%) extended into the perirectal fat, and 6 (3%) reached the
visceral peritoneum. The primary treatment modalities were endoscopic resection (n = 86, 43%) and surgical
extirpation (n = 102, 50%). Forty-one patients (40%) underwent a high anterior resection, whereas 45 (44%)
underwent anterior resection with total mesorectal excision. Seven patients (7%) underwent Hartman's
procedure, 7 (7%) underwent abdomino-perineal resection, and 6 (6%) had transanal endoscopic microsurgery,
whereas 4 (4%) patients underwent a transanal excision. Multiple variable logistic regression analysis
demonstrated that tumor size greater than 10 mm and lymphovascular invasion were predictors of nodal
involvement (P = 0.006 and < 0.001, respectively), whereas the presence of lymph node metastases and
lymphovascular invasion was associated with subsequent development of distant metastases (P = 0.033 and
0.022, respectively). The presence of nodal metastases has a profound effect upon survival, with a 5-year
survival rate of 70%, and 10-year survival of 60% for node positive tumors. Patients with distant metastases
have a 4-year survival of 38%. CONCLUSION: Tumor size greater than 10 mm and lymphovascular invasion are
significantly associated with the presence of nodal disease, rendering mesorectal excision advisable. Transanal
excision is adequate for smaller tumors.
PubMed-ID: 21037430

The Impact of 68Ga-DOTATOC Positron Emission Tomography/Computed Tomography on the
Multimodal Management of Patients With Neuroendocrine Tumors.
Ann Surg, 252(5):850-6.
Frilling A, Sotiropoulos GC, Radtke A, Malago M, Bockisch A, Kuehl H, Li J, Broelsch CE. 2010.
OBJECTIVE: To evaluate the impact of 68Ga-DOTATOC positron emission tomography (PET)/computed
tomography (CT) on the multimodal management of neuroendocrine tumors (NET). BACKGROUND:

ESES Review of Recently Published Literature 2010-3                                             Page 65 of 68
Establishment of the extent and progression of NET are necessary to decide which treatment option to choose.
However, morphological imaging with CT or magnetic resonance imaging (MRI) is often inadequate in identifying
the primary tumor and/or in detecting small metastatic lesions. METHODS: In total, 52 patients (27 women and
25 men) with histologically proven NET could be included in the protocol of comparison between 68Ga-
DOTATOC PET/CT and CT and/or MRI. The examinations were performed in terms of tumor staging and, in
some instances, also of primary tumor site identification to evaluate the patient's eligibility for treatment. Each
patient presented with either CT and/or MRI performed elsewhere and consecutively underwent 68Ga-
DOTATOC PET/CT in our institution. RESULTS: In all 52 patients, 68Ga-DOTATOC PET/CT demonstrated
pathologically increased uptake for at least 1 tumor site, yielding a sensitivity of 100% on a patient basis. In 3 of
4 patients with unknown primary tumor site, 68Ga-DOTATOC PET/CT visualized the primary tumor region
(jejunum, ileum, and pancreas, respectively) not identified on CT and/or MRI. 68Ga-DOTATOC PET/CT
detected additional hepatic and/or extrahepatic metastases in 22 of the 33 patients diagnosed with hepatic
metastases on CT and/or MRI. Of the 15 patients evaluated for liver transplantation, we omitted 7 (46.6%) from
further screening because of evidence of metastatic deposits not seen by conventional imaging. Overall, 68Ga-
DOTATOC PET/CT altered our treatment decision based on CT and/or MRI alone, in 31 (59.6%) of the 52
patients. CONCLUSIONS: In this study, 68Ga-DOTATOC PET/CT proved clearly superior to CT and/or MRI for
detection and staging of NET. More important, 68Ga-DOTATOC PET/CT impacted our treatment decision in
more than every second patient.
PubMed-ID: 21037441

Metastatic Tumors in the Pancreas in the Modern Era.
J Am Coll Surg, 211(6):749-53.
Konstantinidis IT, Dursun A, Zheng H, Wargo JA, Thayer SP, Fernandez-del CC, Warshaw AL, Ferrone CR.
BACKGROUND: Tumors metastasizing to the pancreas are rare, and published series are limited by few
patients treated for extended periods of time. Renal cell cancer (RCC) is the most common primary tumor
metastasizing to the pancreas. Our aim was to describe the clinicopathologic characteristics and patient
outcomes in a modern series of patients who underwent metastasectomy, with an emphasis on RCC. STUDY
DESIGN: Retrospective review of all pancreatic resections between January 1993 and October 2009.
RESULTS: We identified 40 patients with a median age of 62 years; 55% were female. Patients most commonly
presented with abdominal pain (47.5%). Operations performed included 10 pancreaticoduodenectomies, 1
middle, 23 distal, 3 total pancreatectomies, and 3 enucleations. Primary cancers were RCC (n = 20), ovarian (n
= 6), sarcoma (n = 3), colon (n = 3), melanoma (n = 2), and others (n = 6). Median survival for all patients after
metastasectomy was 4.4 years. Median survival after metastasectomy for RCC was 8.7 years, and the 5-year
actuarial survival was 61%. For RCCs, pancreas was the first site of an extrarenal recurrence in 85% and was
synchronous with the primary in 5% of patients. There was no survival difference if the time interval to
metastasis was shorter than the median (8.7 years), if tumor nodules were multiple or bigger than the median (3
cm), or if the pancreas was not the first site of metastases. CONCLUSIONS: An aggressive approach to lesions
metastatic to the pancreas is often warranted if the patient can be rendered free of disease. Although patients
with RCC can experience long-term survival after metastasectomy, survival is less favorable for other primary
PubMed-ID: 21109158

Endocrine Surgery Specialty Training: Opportunities for Growth.
Surgery, 148(6):1073-4.
Libutti SK. 2010.
PubMed-ID: 21134535

Training Our Future Endocrine Surgeons: a Look at the Endocrine Surgery Operative Experience of U.S.
Surgical Residents.
Surgery, 148(6):1075-80.
Zarebczan B, McDonald R, Rajamanickam V, Leverson G, Chen H, Sippel RS. 2010.
BACKGROUND: During the last 10 years, the number of endocrine procedures performed in the United States
has increased significantly. We sought to determine whether this has translated into an increase in operative
volume for general surgery and otolaryngology residents. METHODS: We evaluated records from the Resident
Statistic Summaries of the Residency Review Committee (RRC) for U.S. general surgery and otolaryngology

ESES Review of Recently Published Literature 2010-3                                                  Page 66 of 68
residents for the years 2004-2008, specifically examining data on thyroidectomies and parathyroidectomies.
RESULTS: Between 2004 and 2008, the average endocrine case volume of U.S. general surgery and
otolaryngology residents increased by approximately 15%, but otolaryngology residents performed more than
twice as many operations as U.S. general surgery residents. The growth in case volume was mostly from
increases in the number of thyroidectomies performed by U.S. general surgery and otolaryngology residents
(17.9 to 21.8, P = .007 and 46.5 to 54.4, P = .04). Overall, otolaryngology residents also performed more
parathyroidectomies than their general surgery counterparts (11.6 vs 8.8, P = .007). CONCLUSION: Although
there has been an increase in the number of endocrine cases performed by graduating U.S. general surgery
residents, this is significantly smaller than that of otolaryngology residents. To remain competitive, general
surgery residents wishing to practice endocrine surgery may need to pursue additional fellowship training.
PubMed-ID: 21134536

Laparoscopic Radiofrequency Thermal Ablation of Neuroendocrine Hepatic Metastases: Long-Term
Surgery, 148(6):1288-93.
Akyildiz HY, Mitchell J, Milas M, Siperstein A, Berber E. 2010.
BACKGROUND: Since our first report 13 years ago, laparoscopic radiofrequency ablation has been incorporated
into the treatment algorithm of patients with neuroendocrine liver metastases. The aim of this study is to report
long-term oncologic results. METHODS: Eighty-nine patients with neuroendocrine hepatic metastases
underwent 119 laparoscopic radiofrequency ablation sessions within 13 years. Data were obtained from a
prospective, Institutional Review Board approved database. Univariate Kaplan Meier and multivariate Cox
proportional hazards model were used for statistical analyses. Data are expressed as mean +/- standard error of
the mean. RESULTS: Thirty-five women and 54 men with a mean age of 56 +/- 1.4 years were included in this
study. Tumor types included were carcinoid (n = 55), pancreatic islet cell (n = 23), and medullary thyroid cancer
(n = 11). Mean tumor size was 3.6 +/- 0.2 and the number of lesions was 6 +/- 1. Perioperative morbidity was
6%, and 30-day mortality was 1%. Symptom relief was achieved in 97% of patients after radiofrequency ablation.
Median follow-up was 30 +/- 3 months. Twenty-two percent of patients developed local liver recurrence, 63%
developed new liver lesions, and 59% developed extrahepatic disease in follow-up. Repeat radiofrequency
ablation (27%) and chemoembolization (7%) were used to achieve additional local tumor control in follow up.
Median disease-free survival was 1.3 years and the overall survival was 6 years after radiofrequency ablation.
Liver tumor volume, symptoms, and extrahepatic disease were independent predictors of survival.
CONCLUSION: To our knowledge, this is the largest prospective experience with radiofrequency ablation of
neuroendocrine liver metastases. Effective symptom palliation and long-term local tumor control are possible in
these patients with minimal morbidity.
PubMed-ID: 21134563

The Importance of a Multidisciplinary Approach to Endocrine Tumors.
Surgery, 148(6):1311-2.
Wang TS, Evans DB. 2010.
PubMed-ID: 21134566

Clinical Pathways Improve Hospital Resource Use in Endocrine Surgery.
J Am Coll Surg, 212(1):35-41.
Kulkarni RP, Ituarte PH, Gunderson D, Yeh MW. 2011.
BACKGROUND: Clinical pathways are increasingly adopted to streamline care after elective surgery. Here, we
describe novel clinical pathways developed for endocrine operations (ie, unilateral thyroid lobectomy, total
thyroidectomy, parathyroidectomy) and evaluate their effects on economic end points at a major academic
hospital. STUDY DESIGN: Length of stay (LOS), hospital charges, and hospital costs for 681 patients
undergoing elective endocrine surgery during a 30-month period were compared between patients managed
with or without a specific pathway. Hospital costs were subcategorized by cost center. The analysis arms were
conducted concurrently to control for institutional effects and end points were adjusted for demographic factors
and comorbidity. RESULTS: Clinical pathways were observed to significantly reduce LOS, charges, and costs
for endocrine procedures. LOS was reduced for thyroid lobectomy (nonpathway 1.6 days versus pathway 1.0; p
< 0.001), total thyroidectomy (2.8 versus 1.1; p < 0.0001), and parathyroidectomy (1.6 versus 1.1; p < 0.001).
Nonpathway patients were 6.2 times more likely to be admitted to the intensive care unit than pathway patients
(p < 0.05). Clinical pathways reduced total charges from $21,941 to $17,313 for all cases (21% reduction; p <

ESES Review of Recently Published Literature 2010-3                                               Page 67 of 68
0.0001), with 47% of savings attributable to reduced LOS. Significant improvements were observed for
laboratory use (73% reduction; p < 0.0001) and nonroutine medication administration (73% reduction; p <
0.0001). The readmission rate within 72 hours of discharge was not significantly lower in the pathway group.
CONCLUSIONS: Implementation of clinical pathways improves efficiency of care after elective endocrine
surgery without adversely affecting safety or quality. Because these system measures optimize resource use,
they represent an important component of high-volume subspecialty surgical services.
PubMed-ID: 21123093

ESES Review of Recently Published Literature 2010-3                                             Page 68 of 68

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